Low-affinity anti-Smith antigen B cells are regulated by anergy as opposed to developmental arrest or differentiation to B-1.
Understanding the regulation of B lymphocytes specific for self-Ags targeted in human and murine systemic lupus erythematosus, such as the ribonucleoprotein Smith Ag (Sm), is crucial to understanding the etiology of this autoimmune disease. To address the role of B cell receptor affinity in the regulation of anti-Sm B cells, we generated low-affinity anti-Sm transgenic mice by combining the anti-Sm 2-12H transgene with a V(kappa)8 transgene. In contrast to 2-12H transgenic mice, in which anti-Sm B cells are predominantly splenic transitional, and peritoneal B-1, low-affinity anti-Sm B cells are long-lived B-2 cells and are found in the spleen, lymph nodes, and peritoneum. However, they are unresponsive to LPS in vitro, indicating that they are anergic, although they do not down-regulate IgM and are not excluded from follicles even in the presence of nonautoreactive B cells. Thus, low-affinity anti-Sm B cells appear to have a partial form of anergy. Interestingly, these cells have elevated levels of MHC class II and CD95, but not CD40, CD80, or CD86, suggesting that they are poised to undergo deletion rather than activation upon T cell encounter. These data identify anergy as a mechanism involved in anti-Sm B cell regulation.
Borrero
Michelle
M
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Clarke
Stephen H
SH
D000818:Animals; D000915:Antibody Affinity; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017635:Clonal Anergy; D005803:Genes, Immunoglobulin; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007075:Immunoglobulin M / Q000097:blood; D016130:Immunophenotyping; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D013154:Spleen / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism; D055517:snRNP Core Proteins
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D017411:Ribonucleoproteins, Small Nuclear; C526416:Snrpb protein, mouse; D019014:fas Receptor; D055517:snRNP Core Proteins