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Originally published online as doi:10.1189/jlb.0308162 on December 12, 2008

Published online before print December 12, 2008
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(Journal of Leukocyte Biology. 2009;85:409-417.)
© 2009 by Society for Leukocyte Biology

CCR7-deficient mice develop atypically persistent germinal centers in response to thymus-independent type 2 antigens

Ariel H. Achtman2, Uta E. Höpken, Carola Bernert and Martin Lipp2

Molecular Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

2 Correspondence: Molecular Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092 Berlin, Germany. E-mail: mlipp{at}mdc-berlin.de

ABSTRACT

Thymus-independent type 2 (TI-2) antigens are repetitive antigens capable of eliciting antibody responses without T cell help. They are important in the immune response against encapsulated bacteria and as a rapid first line of defense against pathogens. TI-2 antigens induce strong proliferation in extrafollicular foci. However, any germinal centers forming in response to TI-2 antigens involute synchronously 5 days after immunization. This is thought to be caused by the lack of T cell help. Surprisingly, immunization of mice deficient for the homeostatic chemokine receptor CCR7 with TI-2 antigens resulted not only in the expected, vigorous extrafollicular plasma cell response but also in persisting splenic germinal centers. This was observed for two different TI-2 antigens, heat-killed Streptococcus pneumoniae and (4-hydroxy-3-nitrophenyl)acetyl-Ficoll (NP-Ficoll). Germinal centers induced by TI-2 and thymus-dependent (TD) antigens were located in the periarteriolar area of the white pulp in CCR7 knockout mice, corresponding to the T zone of wild-type (WT) mice. The TI-2-induced germinal centers contained peripheral rings of follicular dendritic cells and unusually for TI-2-induced germinal centers, T cells. The licensing responsible for their atypical persistence did not endow TI-2-induced germinal centers with the full range of characteristics of classic germinal centers induced by TD antigens. Thus, class-switching, affinity maturation, and memory B cell generation were not increased in CCR7-deficient mice. It seems unlikely that a defect in regulatory T cell (Treg) location was responsible for the atypical persistence of TI-2-induced germinal centers, as Tregs were comparably distributed in germinal centers of CCR7-deficient and WT mice.

Key Words: homeostatic chemokine • spleen • antibody • TI-2 • NP-Ficoll




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