Article Text

other Versions

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}


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

Statistics from


  • 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.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.