title: B cell lymphoproliferation and organ-directed self-recognition to explain autoimmunity: back to the past.
abstract: Autoimmune diseases are characterised by lymphoproliferation in target tissues with B and T lymphocytes often arranged in pseudofollicles, mimicking the structure of peripheral lymph nodes. Target organ tissue damage produces the clinical phenotype which may be diverse ranging from autoimmune endocrinopathies to malabsorption (coeliac disease) to structural damage within bones and joints (rheumatoid arthritis). Recently, B cell depletion has been shown to be effective in many autoimmune conditions suggesting a common pathological origin for these conditions which might be triggered by an autoimmune B cell that has escaped deletion. We postulate that a mutation in a transcription factor early in B cell development might allow persistence and foster proliferation of a clone of autoimmune B cells, capable of producing autoantibodies. A similar common mutation within the JAK2 tyrosine kinase gene has recently been described associated with the myeloproliferative disorders which are also characterised by diverse clinical disease phenotypes. There is considerable evidence that autoimmune diseases could be indolent lymphoproliferative disorders of B-cell origin, extending the forbidden clone hypothesis first proposed in the 1950s.
authors.affiliation: Department of Molecular Medicine and Pathology, University of Auckland, P.O. Box 92019, Auckland, New Zealand. f.mcqueen@auckland.ac.nz
authors.forename: Fiona
authors.initials: F
authors.lastname: McQueen
authors.forename: Bob
authors.initials: B
authors.lastname: Elliott
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D049109:Cell Proliferation; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000209:etiology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D014157:Transcription Factors