The regulation and activation of lupus-associated B cells

被引:27
作者
Fields, ML [1 ]
Hondowicz, BD [1 ]
Wharton, GN [1 ]
Adair, BS [1 ]
Metzgar, MH [1 ]
Alexander, ST [1 ]
Caton, AJ [1 ]
Erikson, J [1 ]
机构
[1] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA
关键词
D O I
10.1111/j.0105-2896.2005.00238.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Anti-double-stranded DNA (anti-dsDNA) B cells are regulated in non-autoimmune mice. While some are deleted or undergo receptor editing, a population of anti-dsDNA (VH3H9/V lambda 1) B cells that emigrate into the periphery has also been identified. These cells have an altered phenotype relative to normal B cells in that they have a reduced lifespan, appear developmentally arrested, and localize primarily to the T/B-cell interface in the spleen. This phenotype may be the consequence of immature B cells encountering antigen in the absence of T-cell help. When provided with T-cell help, the anti-dsDNA B cells differentiate into antibody-forming cells. In the context of the autoimmune-prone lpr/lpr or gld/gld mutations, the VH3H9/V lambda 1 anti-dsDNA B cells populate the B-cell follicle and by 12 weeks of age produce serum autoantibodies. The early event of anti-dsDNA B-cell follicular entry, in the absence of autoantibody production, is dependent upon CD4(+) T cells. We hypothesize that control of autoantibody production in young autoimmune-prone mice may be regulated by the counterbalancing effect of T-regulatory (T-reg) cells. Consistent with this model, we have demonstrated that T-reg cells are able to prevent autoantibody production induced by T-cell help. Additional studies are aimed at investigating the mechanisms of this suppression as well as probing the impact of distinct forms of T-cell-dependent and -independent activation on anti-dsDNA B cells.
引用
收藏
页码:165 / 183
页数:19
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