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Originally published online as doi:10.1189/jlb.1203643 on June 14, 2004

Published online before print June 14, 2004
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(Journal of Leukocyte Biology. 2004;76:709-718.)
© 2004 by Society for Leukocyte Biology

Distinct and overlapping roles of CXCR5 and CCR7 in B-1 cell homing and early immunity against bacterial pathogens

Uta E. Höpken1, Ariel H. Achtman, Kerstin Krüger and Martin Lipp

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

1 Correspondence: Max-Delbrück-Center for Molecular Medicine, MDC, Robert-Rössle-Str. 10, 13092 Berlin, Germany. E-mail: uhoepken{at}mdc-berlin.de

CXC chemokine receptor (CXCR)5 and CC chemokine receptor (CCR)7 are the major chemokine receptors required for B cell homing and microenvironmental localization during antigen-independent and -dependent B cell differentiation. Here, we show markedly decreased B-1 B cell numbers in the peritoneal cavity of CXCR5–/– and CXCR5–/–CCR7–/– double-deficient mice paralleled by reduced antigen-induced phosphorylcholine-specific immunoglobulin (Ig)M responses after intraperitoneal (i.p.) administration of streptococcal antigen. CCR7–/– mice also revealed a partial reduction in peritoneal B-1 cell numbers combined with a reduced humoral response to i.p. injected bacterial antigen. However, opposite roles of CXCR5 and CCR7 were observed when the frequency of peritoneal B-2 cells was analyzed. CXCR5–/– mice almost completely lacked B-2 cells, whereas CCR7 deficiency engendered an increase in peritoneal B-2 cells. In addition, CCR7–/– mice had enhanced, splenic IgM+ plasma cell responses, whereas the extrafollicular B cell response of the CXCR5–/–mice was not significantly altered compared with wild-type controls. Thus, the two chemokine receptors exert divergent forces at multiple levels of the innate immune response. CXCR5 plays a dominant role in peritoneal B-1 B cell homing and body cavity immunity, but both chemokine receptors are needed for a proportional peritoneal B-2 cell homing and balanced development of an early splenic B cell response.

Key Words: chemokine receptor • body cavity immunity • B cells • immunoglobulin M




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