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A B cell explanation for autoimmune disease: the forbidden clone returns
  1. Fiona McQueen
  1. Correspondence to Professor Fiona McQueen, Department of Molecular Medicine and Pathology, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand; f.mcqueen{at}auckland.ac.nz

Abstract

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.

  • B cells
  • autoimmune disease
  • rheumatoid arthritis
  • rheumatology
  • MRI
  • immunology

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Footnotes

  • Funding Funding for the author's work cited within this manuscript has been provided from the Auckland Medical Research Foundation.

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

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