Autoreactive MZ and B-1 B-cell activation by Faslpr is coincident with an increased frequency of apoptotic lymphocytes and a defect in macrophage clearance.
Blood
; 108(3): 974-82, 2006 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-16861350
ABSTRACT
Murine autoreactive anti-Smith (Sm) B cells are negatively regulated by anergy and developmental arrest, but are also positively selected into the marginal zone (MZ) and B-1 B-cell populations. Despite positive selection, anti-Sm production occurs only in autoimmune-prone mice. To investigate autoreactive B-cell activation, an anti-Sm transgene was combined with the lpr mutation, a mutation of the proapoptotic gene Fas (Fas(lpr)), on both autoimmune (MRL) and nonautoimmune backgrounds. Fas(lpr) induces a progressive and autoantigen-specific loss of anti-Sm MZ and B-1 B cells in young adult Fas(lpr) and MRL/Fas(lpr) mice that does not require that Fas(lpr) be B-cell intrinsic. This loss is accompanied by a bypass of the early pre-plasma cell (PC) tolerance checkpoint. Although the MRL bkg does not lead to a progressive loss of anti-Sm MZ or B-1 B cells, it induces a robust bypass of the early pre-PC tolerance checkpoint. Fas(lpr) mice have a high frequency of apoptotic lymphocytes in secondary lymphoid tissues and a macrophage defect in apoptotic cell phagocytosis. Since Sm is exposed on the surface of apoptotic cells, we propose that anti-Sm MZ and B-1 B-cell activation is the result of a Fas(lpr)-induced defect in apoptotic cell clearance.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Autoimmunity
/
Apoptosis
/
Fas Receptor
Limits:
Animals
Language:
En
Journal:
Blood
Year:
2006
Type:
Article
Affiliation country:
United States