B-cell-activating factor (BAFF) is a member of the tumour-necrosis factor (TNF) family.
BAFF is a trimeric membrane-bound or soluble factor that binds to three receptors — BCMA (B-cell maturation antigen), TACI (transmembrane activator and calcium-modulator and cyclophilin ligand (CAML) interactor) and BAFF-R (BAFF receptor) — which are all expressed on B cells. TACI and BAFF-R are also detected on T cells. BAFF and APRIL (a proliferation-inducing ligand) — another member of the TNF family — share TACI and BCMA.
BAFF is a survival factor for B cells that controls B-cell maturation. BAFF-deficient mice lack mature B cells. BAFF supports the survival of immature T2 B cells and, possibly, mature B cells, but not B1 B cells.
BAFF-R controls B-cell maturation and TACI controls B-cell homeostasis and T-cell-independent immune responses, whereas the role of BCMA is still unknown.
BAFF costimulates immune B-cell responses. Mice that are transgenic for BAFF have increased numbers of B cells — in particular, T2 and marginal-zone (MZ) B cells — and elevated levels of autoantibodies, and they progressively develop nephritis, as well as a Sjögren's-like syndrome.
MZ-like B cells have been detected in the inflamed tissues of BAFF-transgenic mice, which indicates a direct role for these cells in the pathogenesis of autoimmune disorders.
Elevated levels of BAFF have been detected in the serum of patients with various B-cell-mediated autoimmune disorders. BAFF has a role in the survival and/or growth of B-cell lymphomas.
BAFF is considered to be a prime therapeutic target.
B-cell-activating factor of the tumour-necrosis-factor family (BAFF) enhances B-cell survival — a function that is indispensable for B-cell maturation — and has a role in enhancing immune responses. Moreover, the overexpression of BAFF results in severe autoimmune disorders in mice, and elevated serum levels of BAFF occur in some patients who have autoimmune diseases. The elucidation of the role of BAFF has set the stage for a new approach to the treatment of autoimmune disease.
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We thank C. R. Mackay, L. Girgis, S. Tangye, P. Schneider, I. R. Mackay, S. L. Kalled and J. Gommerman for critical reading of the manuscript and helpful suggestions.
- T HELPER 1/T HELPER 2
(TH1/TH2). At least two distinct subsets of activated CD4+ T cells have been described. TH1 cells produce IFN-γ, lymphotoxin and TNF, and support cell-mediated immunity. TH2 cells produce IL-4, IL-5 and IL-13, support humoral immunity and downregulate TH1 responses.
- MARGINAL-ZONE B CELLS
Mature B cells that are phenotypically and functionally distinct from follicular B cells. They participate early in immune responses.
- B1 COMPARTMENT
A population of self-renewing mature B cells that are enriched in pleural and peritoneal cavities. They recognize a restricted set of antigens, including self-antigens.
- GERMINAL CENTRE
The structure that is formed by the expansion of antigen-activated B cells in the B-cell follicle. B cells in germinal centres proliferate and their immunoglobulin genes undergo somatic hypermutation. Cells exit the germinal centre as memory B cells or plasma cells.
- SYSTEMIC LUPUS ERYTHEMATOSUS
(SLE). A human autoimmune disease of unknown aetiology, in which tissues and cells are damaged by pathogenic anti-bodies and immune-complex deposition. Generally, patients have abnormal T-cell and B-cell function.
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Mackay, F., Browning, J. BAFF: A fundamental survival factor for B cells. Nat Rev Immunol 2, 465–475 (2002). https://doi.org/10.1038/nri844
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