Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches

Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches
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DOI:
10.1016/j.immuni.2004.05.010
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发表时间:
2004-06-01
期刊:
影响因子:
32.4
通讯作者:
Brink, R
Brink, R
中科院分区:
医学1区
文献类型:
--
作者:
Thien, M;Phan, TG;Brink, R

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The role of BAFF in B cell self tolerance was examined by tracking the fate of anti-HEL self-reactive B cells in BAFF transgenic mice using four different models of self-reactive B cell deletion. BAFF overexpression did not affect the development of self-reactive B cells normally deleted in the bone marrow or during the early stages of peripheral development. By contrast, self-reactive B cells normally deleted around the late T2 stage of peripheral development were rescued from deletion, matured, and colonized the splenic follicle. Furthermore, self-reactive B cells normally selectively deleted from the marginal zone repopulated this compartment when excess BAFF was present. Self-reactive B cells rescued by excess BAFF were not anergic. BAFF overexpression therefore rescued only self-reactive B cells normally deleted with relatively low stringency and facilitated their migration into otherwise forbidden microenvironments. This partial subversion of B cell self tolerance is likely to underlie the autoimmunity associated with BAFF overexpression.