¹The Autoimmunity Research Unit, The Garvan Institute of Medical research, Darlinghurst, New South Wales, Australia

Correspondence: Professor F Mackay, Autoimmunity Research Unit, The Garvan Institute of Medical research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. E-mail: f.mackay@garvan.org.au

Received 12 October 2007; Accepted 13 October 2007.

Abstract

Systemic autoimmunity such as systemic lupus erythematosus (SLE) is associated with the loss of B-cell tolerance, B-cell dysregulation and autoantibody production. While some autoantibodies may contribute to the pathology seen with SLE, numerous studies have shown that dysregulation of T-cell function is another critical aspect driving disease. The positive results obtained in clinical trials using T-cell- or B-cell-specific treatments have suggested that cooperation between T and B cells probably underlies disease progression in many patients. A similar cooperative mechanism seemed to explain SLE developing in mice overexpressing the B-cell-activating factor from the tumor necrosis factor family (BAFF). However, surprisingly, T-cell-deficient BAFF transgenic (Tg) mice develop SLE similar to T-cell-sufficient BAFF Tg mice, and the disease was linked to innate activation of B cells and production of proinflammatory autoantibody isotypes. In conclusion, dysregulated innate activation of B cells alone can drive disease independently of T cells, and as such this aspect represents a new pathogenic mechanism in autoimmunity.