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The Journal of Immunology, 2004, 173: 807-817.
Copyright © 2004 by The American Association of Immunologists

B Cell-Activating Factor Belonging to the TNF Family (BAFF)-R Is the Principal BAFF Receptor Facilitating BAFF Costimulation of Circulating T and B Cells1

Lai Guan Ng2,*, Andrew P. R. Sutherland2,*,{dagger}, Rebecca Newton*, Fang Qian§, Teresa G. Cachero§, Martin L. Scott§, Jeffrey S. Thompson§, Julie Wheway*, Tatyana Chtanova*,{dagger}, Joanna Groom*, Ian J. Sutton*, Cynthia Xin*,{dagger}, Stuart G. Tangye{ddagger}, Susan L. Kalled§, Fabienne Mackay*,{dagger} and Charles R. Mackay3,*,{dagger}

* Arthritis and Asthma Research Program, The Garvan Institute of Medical Research, Sydney, {dagger} Cooperative Research Center for Asthma, Sydney, {ddagger} Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia; and § Department of Research, Biogen Idec Inc., Cambridge, MA 02142

BAFF (B cell-activating factor belonging to the TNF family) is a cell survival and maturation factor for B cells, and overproduction of BAFF is associated with systemic autoimmune disease. BAFF binds to three receptors, BAFF-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation Ag (BCMA). Using specific mAbs, BAFF-R was found to be the predominant BAFF receptor expressed on peripheral B cells, in both humans and mice, and antagonist mAbs to BAFF-R blocked BAFF-mediated costimulation of anti-µ responses. The other BAFF receptors showed a much more restricted expression pattern, suggestive of specialized roles. BCMA was expressed by germinal center B cells, while TACI was expressed predominantly by splenic transitional type 2 and marginal zone B cells, as well as activated B cells, but was notably absent from germinal center B cells. BAFF was also an effective costimulator for T cells, and this costimulation occurs entirely through BAFF-R. BAFF-R, but not TACI or BCMA, was expressed on activated/memory subsets of T cells, and T cells from BAFF-R mutant A/WySnJ mice failed to respond to BAFF costimulation. Thus, BAFF-R is important not only for splenic B cell maturation, but is the major mediator of BAFF-dependent costimulatory responses in peripheral B and T cells.




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