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

M Thien, TG Phan, S Gardam, M Amesbury, A Basten… - Immunity, 2004 - cell.com
M Thien, TG Phan, S Gardam, M Amesbury, A Basten, F Mackay, R Brink
Immunity, 2004cell.com
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 …
Abstract
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.
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