Distinct and overlapping roles of CXCR5 and CCR7 in B-1 cell homing and early immunity against bacterial pathogens.
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.
Höpken
Uta E
UE
Department of Tumor Genetics and Immunogenetics, MDC, Robert-Rössle-Str. 10, 13092 Berlin, Germany. uhoepken@mdc-berlin.de
Achtman
Ariel H
AH
Krüger
Kerstin
K
Lipp
Martin
M
D000818:Animals; D000942:Antigens, Bacterial / Q000187:drug effects / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology; D001424:Bacterial Infections / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000942:Antigens, Bacterial; C513179:CXCR5 protein, mouse; C515371:Ccr7 protein, mouse; D007075:Immunoglobulin M; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; C070010:streptococcal beta antigen