Originally published online as doi:10.1189/jlb.0407214 on July 5, 2007
Published online before print July 5, 2007
(Journal of Leukocyte Biology. 2007;82:1027-1032.)
© 2007
by Society for Leukocyte Biology
Polyclonal B cell activation in infections: infectious agents’ devilry or defense mechanism of the host?
Carolina L. Montes,
Eva V. Acosta-Rodríguez,
Maria Cecilia Merino,
Daniela A. Bermejo and
Adriana Gruppi1
Department of Clinical Biochemistry, School of Chemical Science, National University of Córdoba, Córdoba, Argentina
1 Correspondence: CIBICI, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina. E-mail: agruppi{at}mail.fcq.unc.edu.ar
 |
ABSTRACT
|
|---|
Polyclonal B cell activation is not a peculiar characteristic to a particular infection, as many viruses, bacteria, and parasites induce a strong polyclonal B cell response resulting in hyper-
-globulinemia. Here, we discuss the different roles proposed for polyclonal B cell activation, which can be crucial for early host defense against rapidly dividing microorganisms by contributing antibodies specific for a spectrum of conserved structures present in the pathogens. In addition, polyclonal B cell activation can be responsible for maintenance of memory B cell responses because of the continuous, unrestricted stimulation of memory B cells whose antibody production may be sustained in the absence of the antigens binding-specific BCR. Conversely, polyclonal activation can be triggered by microorganisms to avoid the host-specific, immune response by activating B cell clones, which produce nonmicroorganism-specific antibodies. Finally, some reports suggest a deleterious role for polyclonal activation, arguing that it could potentially turn on anti-self-responses and lead to autoimmune manifestations during chronic infections.
Key Words: microorganisms • cytokines • natural antibodies • immunoglobulin • immunopathology
|
INTRODUCTION
|
|---|
It is well documented that some microbial molecules and microorganisms can directly induce the proliferation and differentiation of antibody-secreting cells from different B cells, regardless of their antigen specificity. This phenomenon is known as polyclonal B cell activation. Polyclonal activators have the ability to induce the proliferation of multiple B cell clones and the up-regulation of MHC class II, CD69, CD25, and costimulatory receptor molecules such as CD80 and CD86 on the B cell surface [1
2
3
]. The antibodies secreted by B cells stimulated with polyclonal activators are nonspecific and preferentially recognize heterologous as well as homologous antigens such as actin, myoglobin, myosin, thyroglobulin, and DNA [4
5
6
7
].
The polyclonal B cell activation is not a privative ability of a particular microorganism. In fact, the presence of a strong polyclonal B cell response resulting in hyper--globulinemia and autoantibodies secretion has been described in many animal models of infection with viruses, parasites, and bacteria [8
,9
]. In these models, the isotypic distribution of the serum Ig depends mainly on the infectious agent involved, and the most common pattern is characterized by the increase of serum IgG2 [5
,10
11
12
13
].
|
MICROORGANISM-DERIVED POLYCLONAL B CELL ACTIVATORS AND SIGNALING PATHWAYS
|
|---|
Numerous works have described the ability of different microorganisms to induce polyclonal activation (revised by Reina-San-Martin et al. [9
]). Lately, the study of specific components of each microorganism, ultimately responsible for the polyclonal B cell response, has acquired new relevance, as these components can be potential targets to control the infection’s undesired effects, or they can be used to enhance a natural antibody response.
The polyclonal activators derived from microorganisms are usually components of the cell membranes, the cytosol, or excretion/secretion products. For instance, we have described two soluble Trypanosoma cruzi-derived proteins: a mitochondrial malate dehydrogenase [1
] and a glutamato dehydrogenase (GDH) [14
], which are able to induce polyclonal B cell responses. Furthermore, other T. cruzi proteins, which have been described as polyclonal activators, are an excretory/secretory antigen of 24 kDa [15
] and two cell surface proteins: a proline racemase [9
] and a trans-sialidase [16
] (Fig. 1
). Other parasitic proteins, such as the soluble proteins from Schistosoma japonicum eggs [17
] and the Leishmania major ribosomal protein S3a homologue [18
], also act as polyclonal B cell activators. Further detailed, Donati et al. [19
] identified the exact region, a cystein-rich interdomain region 1 
, of the Plasmodium falciparum erythrocyte membrane protein, which induces the polyclonal activation. The bacterial protein, Staphylococcal protein A (SpA), represents a new class of antigens, which bind to the F(ab) regions of Ig molecules outside their complementarity-determining regions. SpA reacts with the F(ab) of most VH3+ Igs, which are expressed on 30–60% of human peripheral B cells. Therefore, SpA has the potential to activate different B cell clones and to elicit inflammatory responses in vivo [20
]. Other bacterial proteins, such as the 75-kDa cell surface protein from Porphyromonas gingivalis [21
], and viral proteins, such as the HIV-1 glycoprotein gp120 [22
] and the influenza hemagglutinin [23
], also activate multiple, naïve B cell clones, stimulating their differentiation and antibody production.
View larger version (58K):
[in this window]
[in a new window]
|
Figure 1. Polyclonal B cell activation induced by T. cruzi antigens. Surface T. cruzi antigens, such as proline-racemase or released antigens, i.e., transialidase and 24 kDa T. cruzi, can act directly on different clones of B cells inducing proliferation and differentiation into plasma cells, whereas intracellular antigens such as GDH need accessory CD11b+ cells to induce such effects. GDH leads to the production of IL-6, IL-10, and B cell-activating factor of the TNF family (BAFF), which synergize to induce B cell expansion powerfully, and IL-6 and IL-10 drive GDH-induced B cell terminal differentiation into a plasma cell.
|
|
Besides proteins, other chemical structures can trigger polyclonal B cell activation. Thus, the LPS from Escherichia coli or Brucella abortus [24
,25
], N-glycans of the primary envelope glycoprotein from lactate dehydrogenase-elevating virus (LDV) [26
], as well as DNA or oligodeoxynucleotides containing CpG motifs [CpG-oligodeoxynucleotide (ODN)] derived from E. coli [27
], Micrococcus lysodeikticus [28
], Babesia bovis, and T. cruzi stimulate the proliferation of naïve B cells [29
].
The molecular mechanisms triggered by polyclonal activators derived from microorganisms have not been elucidated completely; however, the pathways triggered by CpG-ODN and LPS have been described extensively. Both molecules are able to activate B cells through TLRs [30
]. It has been well demonstrated that the immune stimulatory effect of CpG-ODN requires binding to the intracellular receptor TLR-9. There is some controversy about how CpG-ODN reaches TLR-9, but some data support the idea that cellular uptake of CpG-ODN involves binding to another cell surface protein. The signaling through TLR-9 triggers modifications in cellular redox balance and induction of cell signaling pathways, such as the MAPKs and the transcription factor NF-
B [31
]. Conversely, LPS binds to the LPS-binding protein (LPSBP) to form the LPS/LPSBP complex, which is captured by CD14. This ternary complex LPS/LPSBP/CD14 then associates with the TLR-4-myeloid differentiation protein 2 complex on B cells, initiating signaling pathways, which involve MyD88, and also leads to the activation of NF-B [32
].
|
CELLS AND CYTOKINES PARTICIPATING IN POLYCLONAL B CELL ACTIVATION
|
|---|
Most polyclonal activators induce B cell proliferation without requiring T cell help [1
,9
,14
,16
], but their action can be modulated by accessory cells such as macrophages or dendritic cells (DC). For example, DC and macrophages can be stimulated via TLRs by intact bacteria and bacterial cell wall components to secrete B cell stimulatory cytokines such as IL-1 and IL-6 [33
,34
]. In this sense, it has been reported that a transient production of IL-6, originating mostly from macrophages, occurs after LDV, murine cytomegalovirus (MCMV), or HIV infection. These increased IL-6 levels could initiate a cascade of events producing some of the infection effects on the B cell immune response [35
,36
]. Supporting these findings, IL-6-deficient mice infected with MCMV showed a less-profound B cell activation than the wild-type mice [36
].
IL-15 is another cytokine produced by monocytes/macrophages, which has been shown to stimulate human B cell proliferation and Ig secretion. Kacani et al. [37
] observed that IL-15 induced the proliferation of resting B cells and enhanced the proliferation and Ig secretion of B cells activated with heat-inactivated HIV-1. Therefore, it is likely that IL-15, in concert with other monocyte-derived cytokines, promotes the polyclonal B cell activation associated with HIV infection. More recently, He et al. [22
] reported that HIV gp120 binds to a subset of IgD+ B cells through the mannose C-type lectin receptor (MCLR). In the presence of gp120, MCLR-expressing B cells proliferate, up-regulate activation-induced cytidine deaminase, and undergo class-switch DNA recombination (CSR) from IgM to IgG or IgA in a CD40-independent manner. CSR is enhanced further by IL-4 or IL-10, whereas antibody secretion requires the presence of BAFF, which is produced by monocytes upon CD4, CCR5, and CXCR4 engagement by gp120 and cooperates with IL-4 and IL-10 to up-regulate MCLRs on B cells.
Using a similar mechanism, T. cruzi GDH stimulates polyclonal proliferation and differentiation of naive B cells in a T cell-independent manner but with the absolute requirement of CD11b+ cells [14
]. Moreover, our findings demonstrate that stimulation of CD11b+ cells by GDH leads to the production of IL-6, IL-10, and BAFF, which all synergize to induce B cell expansion powerfully. It is important that IL-6 and IL-10 drive GDH-induced B cell terminal differentiation further into plasma cells by up-regulating critical transcription factors for Ig secretion. Our data provided the first evidence that a protozoan antigen can induce BAFF production by accessory cells triggering, in concert with other cytokines, a polyclonal B cell activation (Fig. 1)
.
It is interesting that it has been described that polyclonal B cell activation induced by some infectious agents requires T cell help. For example, murine infection with -herpes virus 68 leads to a nonspecific B cell activation and antibody production through a CD4+ T cell-dependent process [38
]. 
T cells also play some role in the polyclonal B cell activation elicited by microorganisms. In fact, it has been demonstrated that the polyclonal T cell activation observed after P. falciparum and Toxoplasma gondii infection would have a potential role in the maintenance of the B-lymphoproliferation observed in the acute phase of these infections [39
,40
]. In addition, Munk et al. [41
] have shown that after in vitro stimulation with Paracoccidioides brasiliensis, T cells produce cytokines, which provide help to B cells in the production of P. brasiliensis-specific antibodies as well as in the induction of polyclonal B cell activation. Hunziker et al. [4
] have studied hyper--globulinemia in mice infected with lymphocytic choriomeningitis virus (LCMV), which induces nonspecific Igs as a result of switching natural IgM specificities to IgG. The process is dependent on help from CD4+ T cells, which specifically recognize LCMV peptides presented by B cells on MHC class II molecules. Thus, hyper--globulinemia arise when specific Th cells recognize B cells, which have processed viral antigens irrespective of the BCR specificity.
|
DIFFERENT B CELL SUBPOPULATIONS ARE TARGETS OF POLYCLONAL ACTIVATION
|
|---|
The polyclonal B cell activation observed after infections with microorganisms, such as T. cruzi, T. gondii, Schistosoma mansoni, L. major, influenza virus, HIV, and hepatitis C virus (HCV), is characterized by the expansion of conventional B-2 B cells as well as CD5+ B-1 cells. In mice, the CD5+ B-1 cells are an important source of polyreactive, natural antibodies. The expansion of CD5+ B-1 cells is a common feature of these infections, although the role assigned to this cell population is uncertain. Minoprio et al. [42
] demonstrated that the expansion of these cells is associated with the immunopathology of Chagas’ disease, as BALB/c Xid mice (lacking B-1 cells) are more resistant to T. cruzi infection and do not develop skeletal or cardiac muscle lesions. In agreement, Zuckerman et al. [43
] postulated that the expansion of CD5+ peripheral B cells observed in patients infected with HCV may play a role in the development of HCV-associated autoimmunity. In contrast, Aramaki et al. [44
] proposed that the activation of B-1 B cells in the inflamed gingival tissue of periodontitis patients may serve as a first line of defense by producing polyreactive antibodies. High levels of B-1a B cells and IL-6 and IL-10 in the inflamed gingival tissues of periodontits patients were correlated with elevated serum concentrations of polyreactive IgG to phosphorylcholine, E. coli LPS, and commensal bacteria. Alternatively, in some situations, it appears that CD5+ B cells do not influence the course of disease. In this sense, Babai et al. [45
] demonstrated that depletion of peritoneal CD5+ B cells has no effect on the course of L. major infection in susceptible and resistant mice, indicating that the increase in this B cell subpopulation is not associated with protection or immunopathology.
Other B cells able to respond to polyclonal activators such as LPS and CpG-ODN are the B cells from splenic marginal zone (MZ), which can be distinguished from the other splenic B cells by CD24high, IgMhigh, IgDhigh, CD23– expression, as well as their higher expression of CD21, which binds the C3 degradation product C3d [46
]. Along with B-1 B cells, MZ B cells are considered the main source of natural antibodies. Moreover, they have been described as cells endowed with natural memory, which provide a bridge between innate and adaptative immune responses [47
]. Although MZ B cells respond to LPS and CpG-ODN with faster kinetics in polyclonal B cell responses, they are often outnumbered by follicular B-2 B cells [48
,49
]. MZ B cells also respond with faster kinetics than B-2 B cells to viral particles [50
] and encapsulated bacteria (T cell-independent type 2 antigens) [51
] but not to parasite antigens (Bermejo et al., submitted manuscript).
The real contribution of the different B cell subsets to the polyclonal responses is difficult to estimate, as they lose their unique phenotypic markers upon activation. However, as all subsets respond to the same or different activators, it is likely that all B cells are, to a certain extent, involved in the polyclonal responses to infectious agents.
|
CONTROVERSIAL BIOLOGICAL SIGNIFICANCE OF POLYCLONAL ACTIVATION-INDUCED HYPER--GLOBULINEMIA
|
|---|
Although the phenomenon of B cell polyclonal activation induced by microorganisms was first described more than 15 years ago, it is still debated whether such a response overall produces beneficial or detrimental effects in the host. The role of polyclonal B cell activation is difficult to investigate for several reasons. First, it is not possible to ablate polyclonal activation without comprising an adaptive response. Second, knocking out specific mitogens from pathogens has not been possible to achieve.
Supporting the idea of a detrimental role, the induction of polyclonal activation could be considered a strategy used by microorganisms to avoid the host-specific immune response. This could occur as a result of the activation of B cell clones with irrelevant specificities. In addition, clones of autoreactive B cells can be expanded as a consequence of the polyclonal activation triggered by different infectious agents. These cells may play a pivotal role in the infection physiopathology inducing autoimmune manifestations lastly [8
,52
,53
].
Conversely, polyclonal B cell activation may play an important role in the defense against infections by enhancing natural antibody production. Natural antibodies represent a collection of germ-line-encoded antigen-recognition molecules, which recognizes a conserved pattern in many pathogens and can activate the innate immune system via the classical pathway of complement activation. Therefore, natural antibodies are particularly important following infection with virus or bacteria; they represent a first line of defense when the adaptative response is not established. After polyclonal B cell activation, the levels of the natural antibodies can increase early to keep up with multiplication of the microorganisms, thus containing the pathogen dissemination. In this regard, Ochsenbein et al. [54
] reported a key role of natural antibodies during generalized infections with vesicular stomatitis virus (VSV), LCMV, vaccinia virus, or Listeria monocytogenes. These authors observed that IgM from conventional, specific, pathogen-free and germ-free C57BL/6 mice is protective against lytic infection with VSV in vitro. Furthermore, they studied the influence of natural antibodies on early infections (2 h and 8 h after infection) produced by virus or bacteria in mice totally lacking antibody production or only lacking IgM. The mice deficient in antibody production showed elevated viral or bacterial titers in peripheral, nonlymphatic organs such as liver, kidney, and brain but showed reduced titers in spleen when compared with antibody-competent mice. Their results demonstrated clearly that natural antibodies are required for the control and resolution of these infectious diseases. As polyclonal B cell activation may expand B cells, which produce natural antibodies, this activation could be considered crucial for early host defense against rapidly dividing pathogens and therefore, occupies a place between T-dependent responses and innate immune responses.
Most recently, it has been proposed that microbial polyclonal B cell activation holds a potential benefit for the host by inducing the production of antibodies with multiple specificities, including those specific for pathogens [55
]. In addition, it has been reported that polyclonal stimuli, derived directly from microbes or from bystander stimulation, are responsible for memory B cells maintenance. In this sense, it has been demonstrated that in contrast to naïve B cells, memory B cells proliferate and differentiate into antibody-secreting cells after in vitro stimulation with polyclonal stimuli in the absence of specific antigen. The continuous, unrestricted stimulation of memory B cells has been proposed as a plausible mechanism by which antibody production may be sustained in the absence of a specific antigen [56
]. Supporting this hypothesis, Fondere et al. [57
] found that resting, HIV-specific memory B cells circulate at low levels in the blood of AIDS patients. These cells can be expanded and quantified by their anti-HIV-1 antibody secretion after a strong polyclonal B cell stimulation. It is interesting that Matter et al. [58
] have proposed that polyclonal B cell activation helps to optimize the memory cytotoxic T lymphocyte (CTL) response against viruses, which are controlled predominantly by CTL. The authors found that LCMV infection in mice induced and maintained a pool of CD27+ memory CTL. CD27 has been defined as a T and B cell coestimulatory molecule whose activity is governed by its ligand CD70, and CD70 expression is tightly regulated and is only transiently expressed on activated T and B cells as well as on subsets of professional APCs. Infection of B cell-deficient mice and CD70-blocking experiments suggested that CD27+ memory CTL were selected positively by interacting with CD70 expressed on polyclonal-activated B cells. Ligation of CD27 on memory CTL increased secondary expansion in vitro and in vivo. Moreover, CD27+ memory CTL were efficient in protecting against a reinfection in vivo. Taken together, these results highlight a novel B cell–CTL interaction during viral infection and a beneficial role of polyclonal B cell activation.
|
CONCLUSION AND FUTURE PERSPECTIVES
|
|---|
As suggested by the above discussion, microbial components able to induce polyclonal B cell responses offer a wide range of function, which can be profited to enhance host humoral immune responses or to restrict the detrimental effects of many infections. However, a better understanding of the biology of polyclonal activators is required to design novel strategies of immunointervention.
Other important issues that remain obscure are the specific receptors and intracellular pathways triggered by many polyclonal activators. In contrast to conventional antigens that exhibit a clonal specificity toward B cells, the substances inducing polyclonal activation favor the expansion of multiple clones of B cells, independent of their BCR specificity. As these microbial components display distinct molecular structures but induce similar effect in the B cells, it is likely that they bind to different receptors but trigger matching pathways of activation.
|
ACKNOWLEDGEMENTS
|
|---|
This work was supported by grants from "Consejo de Investigaciones Científicas y Técnicas (CONICET)," SECyT-UNC, and "Agencia Nacional de Promoción Científica y Técnica (PICT 05-14575)" to A. G.
Received April 8, 2007;
revised June 5, 2007;
accepted June 11, 2007.
|
REFERENCES
|
|---|
- Montes, C. L., Zuniga, E. I., Vazquez, J., Arce, C., Gruppi, A. (2002) Trypanosoma cruzi mitochondrial malate dehydrogenase triggers polyclonal B-cell activation Clin. Exp. Immunol. 127,27-36[CrossRef][Medline]
- Rott, O., Mignon-Godefroy, K., Fleischer, B., Charreire, J., Cash, E. (1995) Superantigens induce primary T cell responses to soluble autoantigens by a non-V β-specific mechanism of bystander activation Cell. Immunol. 161,158-165[CrossRef][Medline]
- Nashar, T. O., Hirst, T. R., Williams, N. A. (1997) Modulation of B-cell activation by the B subunit of Escherichia coli enterotoxin: receptor interaction up-regulates MHC class II, B7, CD40, CD25 and ICAM-1 Immunology 91,572-578[CrossRef][Medline]
- Hunziker, L., Recher, M., Macpherson, A. J., Ciurea, A., Freigang, S., Hengartner, H., Zinkernagel, R. M. (2003) Hyperglobulinemia and autoantibody induction mechanisms in viral infections Nat. Immunol. 4,343-349[CrossRef][Medline]
- Silva, E. E., Ramos, O. P., Bauab, T. M., Falcao, D. P., de Medeiros, B. M. (2003) Yersinia enterocolitica O:3 isolated from patients with or without reactive arthritis induces polyclonal activation of B cells and autoantibody production in vivo Autoimmunity 36,261-268[CrossRef][Medline]
- Montes, C. L., Vottero-Cima, E., Gruppi, A. (1996) Trypanosoma cruzi cytosolic alkaline antigens (FI) induce polyclonal activation in murine normal B cells Scand. J. Immunol. 44,93-100[CrossRef][Medline]
- Montes, C. L., Zuniga, E., Minoprio, P., Vottero-Cima, E., Gruppi, A. (1999) A Trypanosoma cruzi alkaline antigen induces polyclonal B-cell activation of normal murine spleen cells by T-cell-independent, BCR-directed stimulation Scand. J. Immunol. 50,159-166[CrossRef][Medline]
- Ramos, O. P., Silva, E. E., Falcao, D. P., de Medeiros, B. M. (2005) Production of autoantibodies associated with polyclonal activation in Yersinia enterocolitica O: 8-infected mice Microbiol. Immunol. 49,129-137[Medline]
- Reina-San-Martin, B., Cosson, A., Minoprio, P. (2000) Lymphocyte polyclonal activation: a pitfall for vaccine design against infectious agents Parasitol. Today 16,62-67[CrossRef][Medline]
- Li, X., Hu, B., Harty, J., Even, C., Plagemann, P. G. (1990) Polyclonal B cell activation of IgG2a and IgG2b production by infection of mice with lactate dehydrogenase-elevating virus is partly dependent on CD4+ lymphocytes Viral Immunol. 3,273-288[Medline]
- Lardans, V., Godfraind, C., van der Logt, J. T., Heessen, W. A., Gonzalez, M. D., Coutelier, J. P. (1996) Polyclonal B lymphocyte activation induced by mouse hepatitis virus A59 infection J. Gen. Virol. 77,1005-1009[Abstract/Free Full Text]
- Stellrecht, K. A., Vella, A. T. (1992) Evidence for polyclonal B cell activation as the mechanism for LCMV-induced autoimmune hemolytic anemia Immunol. Lett. 31,273-277[CrossRef][Medline]
- Price, P., Olver, S. D., Gibbons, A. E., Shellam, G. R. (1993) B-cell activation following murine cytomegalovirus infection: implications for autoimmunity Immunology 78,14-21[Medline]
- Montes, C. L., Acosta-Rodriguez, E. V., Mucci, J., Zuniga, E. I., Campetella, O., Gruppi, A. (2006) A Trypanosoma cruzi antigen signals CD11b+ cells to secrete cytokines that promote polyclonal B cell proliferation and differentiation into antibody-secreting cells Eur. J. Immunol. 36,1474-1485[CrossRef][Medline]
- Da Silva, A. C., Espinoza, A. G., Taibi, A., Ouaissi, A., Minoprio, P. (1998) A 24,000 MW Trypanosoma cruzi antigen is a B-cell activator Immunology 94,189-196[CrossRef][Medline]
- Gao, W., Wortis, H. H., Pereira, M. A. (2002) The Trypanosoma cruzi trans-sialidase is a T cell-independent B cell mitogen and an inducer of non-specific Ig secretion Int. Immunol. 14,299-308[Abstract/Free Full Text]
- Yamashita, T., Watanabe, T., Saito, S., Araki, Y., Sendo, F. (1993) Schistosoma japonicum soluble egg antigens activate naive B cells to produce antibodies: definition of parasite mechanisms of immune deviation Immunology 79,189-195[Medline]
- Cordeiro-Da-Silva, A., Borges, M. C., Guilvard, E., Ouaissi, A. (2001) Dual role of the Leishmania major ribosomal protein S3a homologue in regulation of T- and B-cell activation Infect. Immun. 69,6588-6596[Abstract/Free Full Text]
- Donati, D., Mok, B., Chene, A., Xu, H., Thangarajh, M., Glas, R., Chen, Q., Wahlgren, M., Bejarano, M. T. (2006) Increased B cell survival and preferential activation of the memory compartment by a malaria polyclonal B cell activator J. Immunol. 177,3035-3044[Abstract/Free Full Text]
- Anderson, A. L., Sporici, R., Lambris, J., Larosa, D., Levinson, A. I. (2006) Pathogenesis of B-cell superantigen-induced immune complex-mediated inflammation Infect. Immun. 74,1196-1203[Abstract/Free Full Text]
- Watanabe, K., Kumada, H., Yoshimura, F., Umemoto, T. (1996) The induction of polyclonal B-cell activation and interleukin-1 production by the 75-kDa cell surface protein from Porphyromonas gingivalis in mice Arch. Oral Biol. 41,725-731[CrossRef][Medline]
- He, B., Qiao, X., Klasse, P. J., Chiu, A., Chadburn, A., Knowles, D. M., Moore, J. P., Cerutti, A. (2006) HIV-1 envelope triggers polyclonal Ig class switch recombination through a CD40-independent mechanism involving BAFF and C-type lectin receptors J. Immunol. 176,3931-3941[Abstract/Free Full Text]
- Rott, O., Charreire, J., Cash, E. (1996) Influenza A virus hemagglutinin is a B cell-superstimulatory lectin Med. Microbiol. Immunol. 184,185-193[CrossRef][Medline]
- Moreno, E., Berman, D. T., Boettcher, L. A. (1981) Biological activities of Brucella abortus lipopolysaccharides Infect. Immun. 31,362-370[Abstract/Free Full Text]
- Koga, T., Nishihara, T., Fujiwara, T., Nisizawa, T., Okahashi, N., Noguchi, T., Hamada, S. (1985) Biochemical and immunobiological properties of lipopolysaccharide (LPS) from Bacteroides gingivalis and comparison with LPS from Escherichia coli Infect. Immun. 47,638-647[Abstract/Free Full Text]
- Plagemann, P. G., Jones, Q. A., Cafruny, W. A. (2000) N-glycans on the short ectodomain of the primary envelope glycoprotein play a major role in the polyclonal activation of B cells by lactate dehydrogenase-elevating virus J. Gen. Virol. 81,2167-2175[Abstract/Free Full Text]
- He, B., Qiao, X., Cerutti, A. (2004) CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10 J. Immunol. 173,4479-4491[Abstract/Free Full Text]
- Neujahr, D. C., Reich, C. F., Pisetsky, D. S. (1999) Immunostimulatory properties of genomic DNA from different bacterial species Immunobiology 200,106-119[Medline]
- Shoda, L. K., Kegerreis, K. A., Suarez, C. E., Roditi, I., Corral, R. S., Bertot, G. M., Norimine, J., Brown, W. C. (2001) DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T. brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor , and nitric oxide Infect. Immun. 69,2162-2171[Abstract/Free Full Text]
- Schnare, M., Holt, A. C., Takeda, K., Akira, S., Medzhitov, R. (2000) Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88 Curr. Biol. 10,1139-1142[CrossRef][Medline]
- Krieg, A. M. (2002) CpG motifs in bacterial DNA and their immune effects Annu. Rev. Immunol. 20,709-760[CrossRef][Medline]
- Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., Akira, S. (1999) Cutting edge:Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the LPS gene product J. Immunol. 162,3749-3752[Abstract/Free Full Text]
- Riva, S., Nolli, M. L., Lutz, M. B., Citterio, S., Girolomoni, G., Winzler, C., Ricciardi-Castagnoli, P. (1996) Bacteria and bacterial cell wall constituents induce the production of regulatory cytokines in dendritic cell clones J. Inflamm. 46,98-105[Medline]
- Aiba, S., Tagami, H. (1998) Dendritic cell activation induced by various stimuli, e.g. exposure to microorganisms, their products, cytokines, and simple chemicals as well as adhesion to extracellular matrix J. Dermatol. Sci. 20,1-13[CrossRef][Medline]
- Markine-Goriaynoff, D., Nguyen, T. D., Bigaignon, G., Van Snick, J., Coutelier, J. P. (2001) Distinct requirements for IL-6 in polyclonal and specific Ig production induced by microorganisms Int. Immunol. 13,1185-1192[Abstract/Free Full Text]
- Karupiah, G., Sacks, T. E., Klinman, D. M., Fredrickson, T. N., Hartley, J. W., Chen, J. H., Morse, H. C., III (1998) Murine cytomegalovirus infection-induced polyclonal B cell activation is independent of CD4+ T cells and CD40 Virology 240,12-26[CrossRef][Medline]
- Kacani, L., Sprinzl, G. M., Erdei, A., Dierich, M. P. (1999) Interleukin-15 enhances HIV-1-driven polyclonal B-cell response in vitro Exp. Clin. Immunogenet. 16,162-172[CrossRef][Medline]
- Stevenson, P. G., Doherty, P. C. (1999) Non-antigen-specific B-cell activation following murine herpesvirus infection is CD4 independent in vitro but CD4 dependent in vivo J. Virol. 73,1075-1079[Abstract/Free Full Text]
- De Paoli, P., Basaglia, G., Gennari, D., Crovatto, M., Modolo, M. L., Santini, G. (1992) Phenotypic profile and functional characteristics of human and T cells during acute toxoplasmosis J. Clin. Microbiol. 30,729-731[Abstract/Free Full Text]
- Ho, M., Tongtawe, P., Kriangkum, J., Wimonwattrawatee, T., Pattanapanyasat, K., Bryant, L., Shafiq, J., Suntharsamai, P., Looareesuwan, S., Webster, H. K., Elliott, J. F. (1994) Polyclonal expansion of peripheral T cells in human Plasmodium falciparum malaria Infect. Immun. 62,855-862[Abstract/Free Full Text]
- Munk, M. E., Fazioli, R. A., Calich, V. L., Kaufmann, S. H. (1995) Paracoccidioides brasiliensis-stimulated human / T cells support antibody production by B cells Infect. Immun. 63,1608-1610[Abstract]
- Minoprio, P., Coutinho, A., Spinella, S., Hontebeyrie-Joskowicz, M. (1991) Xid immunodeficiency imparts increased parasite clearance and resistance to pathology in experimental Chagas’ disease Int. Immunol. 3,427-433[Abstract/Free Full Text]
- Zuckerman, E., Slobodin, G., Kessel, A., Sabo, E., Yeshurun, D., Halas, K., Toubi, E. (2002) Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection Clin. Exp. Immunol. 128,353-358[CrossRef][Medline]
- Aramaki, M., Nagasawa, T., Koseki, T., Ishikawa, I. (1998) Presence of activated B-1 cells in chronic inflamed gingival tissue J. Clin. Immunol. 18,421-429[CrossRef][Medline]
- Babai, B., Louzir, H., Cazenave, P. A., Dellagi, K. (1999) Depletion of peritoneal CD5+ B cells has no effect on the course of Leishmania major infection in susceptible and resistant mice Clin. Exp. Immunol. 117,123-129[CrossRef][Medline]
- Timens, W., Boes, A., Poppema, S. (1989) Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation Eur. J. Immunol. 19,2163-2166[Medline]
- Martin, F., Kearney, J. F. (2000) B-cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a "natural immune memory" Immunol. Rev. 175,70-79[CrossRef][Medline]
- Brummel, R., Lenert, P. (2005) Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides J. Immunol. 174,2429-2434[Abstract/Free Full Text]
- Oliver, A. M., Martin, F., Kearney, J. F. (1999) IgMhighCD21high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells J. Immunol. 162,7198-7207[Abstract/Free Full Text]
- Gatto, D., Ruedl, C., Odermatt, B., Bachmann, M. F. (2004) Rapid response of marginal zone B cells to viral particles J. Immunol. 173,4308-4316[Abstract/Free Full Text]
- Martin, F., Oliver, A. M., Kearney, J. F. (2001) Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens Immunity 14,617-629[CrossRef][Medline]
- Minoprio, P., Burlen, O., Pereira, P., Guilbert, B., Andrade, L., Hontebeyrie-Joskowicz, M., Coutinho, A. (1988) Most B cells in acute Trypanosoma cruzi infection lack parasite specificity Scand. J. Immunol. 28,553-561[CrossRef][Medline]
- Granholm, N. A., Cavallo, T. (1992) Autoimmunity, polyclonal B-cell activation and infection Lupus 1,63-74[Abstract/Free Full Text]
- Ochsenbein, A. F., Fehr, T., Lutz, C., Suter, M., Brombacher, F., Hengartner, H., Zinkernagel, R. M. (1999) Control of early viral and bacterial distribution and disease by natural antibodies Science 286,2156-2159[Abstract/Free Full Text]
- Ochsenbein, A. F., Pinschewer, D. D., Odermatt, B., Carroll, M. C., Hengartner, H., Zinkernagel, R. M. (1999) Protective T cell-independent antiviral antibody responses are dependent on complement J. Exp. Med. 190,1165-1174[Abstract/Free Full Text]
- Bernasconi, N. L., Traggiai, E., Lanzavecchia, A. (2002) Maintenance of serological memory by polyclonal activation of human memory B cells Science 298,2199-2202[Abstract/Free Full Text]
- Fondere, J. M., Huguet, M. F., Macura-Biegun, A., Baillat, V., Ohayon, V., Reynes, J., Vendrell, J. P. (2004) Detection and enumeration of circulating HIV-1-specific memory B cells in HIV-1-infected patients J. Acquir. Immune Defic. Syndr. 35,114-119[CrossRef][Medline]
- Matter, M., Mumprecht, S., Pinschewer, D. D., Pavelic, V., Yagita, H., Krautwald, S., Borst, J., Ochsenbein, A. F. (2005) Virus-induced polyclonal B cell activation improves protective CTL memory via retained CD27 expression on memory CTL Eur. J. Immunol. 35,3229-3239[CrossRef][Medline]
TOP
ABSTRACT
INTRODUCTION
