Immunology

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Science  10 May 2002:
Vol. 296, Issue 5570, pp. 985
DOI: 10.1126/science.296.5570.985b

Under normal circumstances, self-reactive B cells that escape deletion are prevented from producing autoantibodies through the induction of a functionally inactive state known as anergy. The risk posed by the anergic route of tolerance is evident, however, when these B cells are occasionally reactivated, resulting in autoantibody production and pathology.

Seo et al. examined the influence of two T cell populations on an autoantibody response directed at double-stranded DNA (dsDNA), a common target in B cell autoimmunity. In the autoimmune lpr/lpr strain of mice, which is prone to developing antibodies to dsDNA, B cells appear to lose tolerance in two distinct stages. In the first, they acquire an altered phenotype, but only generate antibodies during a later second phase. In trying to understand this pattern of autoimmunity, mice expressing a transgene for an antibody to dsDNA were used. B cells from these mice lost their anergic state upon injection of helper T cells. However, co-administration of CD4+CD25+ regulatory T cells produced only the first “abortive” stage of anergy loss seen in lpr mice. This second tier of modulation of the B cell anergy requiring regulation of T cell help may prove an important checkpoint in preventing autoimmunity.—SJS

Immunity16, 535 (2002).

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