The germinal center response is impaired in the absence of T cell-expressed CXCR5.
Germinal centers support the differentiation of memory B cells and long-lived antibody-secreting cells during infection or upon vaccination. Here, we constructed mice with T cells that selectively lack the chemokine receptor CXCR5 to determine if expression of this receptor by T cells is mandatory for germinal center formation and function. In these animals, germinal centers that are properly localized in B cell follicles and contain T cells do form after immunization with a thymus-dependent antigen. However, fewer and smaller germinal centers form, resulting in a significant reduction in the frequency of germinal center B cells. The defect in germinal center formation is paralleled by decreased frequencies of isotype-switched antibody-secreting cells in the spleen and bone marrow and reduced serum concentrations of total and high-affinity hapten-specific IgG1. The results demonstrate that although CXCR5-dependent T cell positioning is important for maximal induction and expansion of germinal centers, stimulation of isotype class switching, and development of antibody-secreting cells that seed the spleen and bone marrow, it is not absolutely required for the formation and function of follicular germinal centers.
Arnold
Carrie N
CN
Department of Pathology, Laboratory of Immunology and Vascular Biology, Stanford University School of Medicine, Stanford, CA, USA. cnarnold@scripps.edu
Campbell
Daniel J
DJ
Lipp
Martin
M
Butcher
Eugene C
EC
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000172:deficiency* / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
C513179:CXCR5 protein, mouse; D007132:Immunoglobulin Isotypes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine