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

Marilyn Thien, Tri Giang Phan, Sandra Gardam, Michelle Amesbury, Antony Basten, Fabienne Mackay, Robert Brink

Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag Number 6, Newtown, New South Wales 2042, Australia.

Immunity 2004 Jun

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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.

Citation

Marilyn Thien, Tri Giang Phan, Sandra Gardam, Michelle Amesbury, Antony Basten, Fabienne Mackay, Robert Brink. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity. 2004 Jun;20(6):785-98