BAFF supports human B cell differentiation in the lymphoid follicles through distinct receptors.
B cell-activating factor of the tumor necrosis factor family (BAFF/BLys) plays a critical role in B cell survival and immune responses through its three receptors: BAFF receptor (BAFF-R/BR3), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA). Using specific antibodies, we have investigated the expression of BAFF-R on human tonsillar B cells and their functional roles in naive and germinal center (GC) B cell differentiation. Our studies show that BAFF-R is the dominant receptor on naive B cells. However, three receptors are differentially modulated during in vitro GC-B cell differentiation. BAFF-R expression increased initially and then decreased with a corresponding induction of TACI and BCMA expression during differentiation to plasma cells (PCs). Consistently, blocking of BAFF-R alone with specific mAb inhibited GC-B cell proliferation and PC generation in the early period of their differentiation, whereas depletion of BAFF with TACI-Ig exhibited consistent inhibition throughout the differentiation. Finally, histological and molecular analyses of human tonsil tissue revealed that follicular dendritic cells produce BAFF. In conclusion, BAFF in the GC plays an important role through more than one receptor, and the three known receptors are differentially modulated as GC-B cells differentiate to PCs.
Zhang
Xin
X
Department of Cellular Immunology, Ochsner Clinic Foundation, 1516 Jefferson Highway, New Orleans, LA, USA.
Park
Chan-Sik
CS
Yoon
Sun-Ok
SO
Li
Li
L
Hsu
Yen-Ming
YM
Ambrose
Christine
C
Choi
Yong Sung
YS
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D014066:Palatine Tonsil / Q000276:immunology; D011971:Receptors, Immunologic / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha