A B cell explanation for autoimmune disease: the forbidden clone returns.
More than 60 years ago, Burnet first proposed the 'forbidden clone' hypothesis postulating that autoimmune disease arises as a result of persistence of self-reactive clones of lymphocytes that should have been deleted via immune tolerance. These autoreactive clones could effect immune-mediated end-organ damage via peripheral self-antigen recognition. Recent evidence that stretches across the boundaries of many medical specialties supports this proposal, implicating a B cell precursor as the culprit. The success of B cell depleting therapy in rheumatoid arthritis, anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis, polymyositis, lupus and autoimmune diseases as diverse as multiple sclerosis and idiopathic thrombocytopenic purpura supports this proposal. Clonality of B cells and plasma cells has been described in a number of autoimmune disorders and the presence of autoantibodies, which may arise years before the onset of clinical disease, supports the notion of autoreactivity within the B cell lineage. T cell activation within the end-organ would be predicted by cognate B-T cell interactions and resultant tissue inflammation and destruction could produce diverse clinical manifestations dictated by the original specificity of the autoimmune B cell.
Department of Molecular Medicine and Pathology, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand. f.mcqueen@auckland.ac.nz
Fiona
F
McQueen
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000382:microbiology*; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002999:Clone Cells; D006801:Humans; D009154:Mutation / Q000235:genetics
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies