Cutting edge: germinal centers formed in the absence of B cell-activating factor belonging to the TNF family exhibit impaired maturation and function.
Germinal centers (GCs) form in B cell follicles and require specific signals for development and maintenance. B cell-activating factor belonging to the TNF family (BAFF) is a fundamental B cell survival factor and therefore may influence GC reactions and subsequent Ab responses. To test this possibility, the effect of BAFF neutralization in immunized mice was assessed. Using B cell maturation Ag-Fc, we demonstrate that BAFF blockade does not inhibit GC formation or somatic hypermutation. However, GCs in B cell maturation Ag-Fc-treated mice dissipated more rapidly than those of control mice and did not form a mature follicular dendritic cell reticulum. Examination of immunized BAFF-null mice validated the BAFF-independent nature of GC formation. Furthermore, Ab responses, including high-affinity responses, were attenuated. This is the first evidence that BAFF is required for maintenance, but not initiation, of the GC reaction, and it further hints that somatic hypermutation within the GC and selection of Ag-specific high-affinity Ab could be uncoupled.
Vora
Kalpit A
KA
Department of Immunology and Inflammation, Biogen, Inc., Cambridge, MA 02142, USA.
Wang
Li Chun
LC
Rao
Sambasiva P
SP
Liu
Zhong-Ying
ZY
Majeau
Gerard R
GR
Cutler
Anne H
AH
Hochman
Paula S
PS
Scott
Martin L
ML
Kalled
Susan L
SL
D000818:Animals; D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family / Q000235:genetics / Q000276:immunology*; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D007074:Immunoglobulin G; D008565:Membrane Proteins; D009596:Nitrophenols; D010648:Phenylacetates; D018124:Receptors, Tumor Necrosis Factor; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; C490176:Tnfrsf17 protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; C026242:4-hydroxy-5-nitrophenyl acetic acid