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

• DOI: 10.4049/jimmunol.173.2.807
• Publication Date: 2014-04-20T23:37:22Z
• Authors: Lai Guan Ng; Andrew P. R. Suth...; Rebecca Newton; Fang Qian; Teresa G. Cachero; Martin L. Scott; Jeffrey S. Thompson; Julie Wheway; Tatyana Chtanova; Joanna Groom; Ian J. Sutton; Cynthia Xin; Stuart G. Tangye; Susan L. Kalled; Fabienne Mackay; Charles R. Mackay
• Keywords: 0301 basic medicine; B-Lymphocytes; Tumor Necrosis Factor-alpha; T-Lymphocytes; Antibodies, Monoclonal; Membrane Proteins; Receptors, Tumor Necrosis Factor; Mice; 03 medical and health sciences; B-Cell Activating Factor; Animals; Humans; B-Cell Activation Factor Receptor

Abstract 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.