title: 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.
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- micro 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.
authors.affiliation: Arthritis and Asthma Research Program, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.forename: Andrew P R
authors.initials: AP
authors.lastname: Sutherland
authors.forename: Rebecca
authors.initials: R
authors.lastname: Newton
authors.forename: Fang
authors.initials: F
authors.lastname: Qian
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Cachero
authors.forename: Martin L
authors.initials: ML
authors.lastname: Scott
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Thompson
authors.forename: Julie
authors.initials: J
authors.lastname: Wheway
authors.forename: Tatyana
authors.initials: T
authors.lastname: Chtanova
authors.forename: Joanna
authors.initials: J
authors.lastname: Groom
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Sutton
authors.forename: Cynthia
authors.initials: C
authors.lastname: Xin
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kalled
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha