International Immunology Advance Access originally published online on May 20, 2005
International Immunology 2005 17(6):779-788; doi:10.1093/intimm/dxh259
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BAFF supports human B cell differentiation in the lymphoid follicles through distinct receptors
1 Department of Cellular Immunology, Ochsner Clinic Foundation, 1516 Jefferson Highway, New Orleans, LA, USA
2 Department of Protein Engineering and 3 Department of Gene Discovery, Biogen Idec, 12 Cambridge Center, Cambridge, MA, USA
Correspondence to: Y. S. Choi; E-mail: ychoi{at}ochsner.org
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.
Keywords: BAFF, BAFF receptors, B cell differentiation, follicular dendritic cells
* These authors contributed equally to this work.
Transmitting editor: C. J. Paige
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