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.
From: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, 27599, USA.
Blood
- Publish Date: Aug 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 3
- Pages: 974-82
- Medium: Print
- Language: English
- Citation (JAMA): Qian Ye, Conway Kara L, Lu Xiangdong, et al. 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 Aug 2006;108:974-82
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.
Mesh Headings (Keywords): Animals, Antibody Formation, Antigens, CD95, Apoptosis, Autoimmunity, B-Lymphocytes, Lymph Nodes, Lymphocyte Activation, Lymphocytes, Macrophages, Mice, Mice, Inbred Strains, Mutation, Phagocytosis
Check for Full Text / PubMed Unique Identifier (PMID): 16861350
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