Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches.
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.
Thien
Marilyn
M
Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag Number 6, Newtown, New South Wales 2042, Australia.
Phan
Tri Giang
TG
Gardam
Sandra
S
Amesbury
Michelle
M
Basten
Antony
A
Mackay
Fabienne
F
Brink
Robert
R
D000818:Animals; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D017635:Clonal Anergy; D017637:Clonal Deletion; D005434:Flow Cytometry; D015870:Gene Expression; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D053264:B-Cell Activating Factor; D008565:Membrane Proteins; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha