Possible roles of B lymphocyte activating factor of the tumour necrosis factor family in vitiligo autoimmunity

Vitiligo is a cutaneous pigmentary disorder characterized by the loss of epidermal melanocytes. Strong evidence supports the theory that autoimmune mechanisms, namely B cell auto-antibody production and auto-reactive T cell cytotoxicity, are involved in this affliction. It is well known that autoimmunity results from a breakdown of self-tolerance. However, the mechanism which leads to the break-down of self-tolerance and subsequently causes the development of autoimmunity in vitiligo remains obscure. B lymphocyte activating factor of the tumour necrosis factor family is a recently identified ligand that is required for peripheral B-cell survival and homeostasis, the excessive production of which may lead to autoimmunity. Based on a collection of indirect evidences, we postulate that in individuals predisposed through inheritance, over-expression of the B lymphocyte activating factor may cause a breakdown of self-tolerance and subsequently cause autoimmune vitiligo via several possible mechanisms: B lymphocyte activating factor activates self-reactive B cells to produce auto-antibodies against melanocytes; these B cells may function as cellular adjuvants for the activation of the CD4+ T cells, enhancing their helper effect on the activation of the CD8+ T cells; CD4+ T cells assist CD8+ T cells to respond to melanocytes antigen, leading to the autoreactive reaction; B lymphocyte activating factor activated B cells capture antigen and present it directly to the CD8+ T cells; and. B lymphocyte activating factor delivers a complete costimulation signal to the T cells (both CD4+ and CD8+ subset), playing an additional role in the autoimmune response in vitiligo. Future challenges remain to test these propositions. Advancement in the treatment of vitiligo is still unsatisfactory, and thus novel modalities of therapy need to be developed. Recently, B lymphocyte activating factor has been evaluated as an attractive target for immune therapy. Once the hypothesis of B lymphocyte activating factor mediating the breakdown of self-tolerance in vitiligo is corroborated, it can become a novel target for treatment of vitiligo. (C) 2010 Elsevier Ltd. All rights reserved.