Cracking the BAFF code.
The tumour necrosis factor (TNF) family members B cell activating factor (BAFF) and APRIL (a proliferation-inducing ligand) are crucial survival factors for peripheral B cells. An excess of BAFF leads to the development of autoimmune disorders in animal models, and high levels of BAFF have been detected in the serum of patients with various autoimmune conditions. In this Review, we consider the possibility that in mice autoimmunity induced by BAFF is linked to T cell-independent B cell activation rather than to a severe breakdown of B cell tolerance. We also outline the mechanisms of BAFF signalling, the impact of ligand oligomerization on receptor activation and the progress of BAFF-depleting agents in the clinical setting.
Mackay
Fabienne
F
Department of Immunology, Monash University, Alfred Hospital, Melbourne, Victoria, Australia. f.mackay@med.monash.edu.au
Schneider
Pascal
P
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D053264:B-Cell Activating Factor / Q000276:immunology* / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000276:immunology / Q000378:metabolism
D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D008024:Ligands; D051193:Toll-Like Receptors; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins