Anti-Sm B cell differentiation in Ig transgenic MRL/Mp-lpr/lpr mice: altered differentiation and an accelerated response.
To determine the regulation of B cells specific for the ribonucleoprotein Sm, a target of the immune system in human and mouse lupus, we have generated mice carrying an anti-Sm H chain transgene (2-12H). Anti-Sm B cells in nonautoimmune 2-12H-transgenic (Tg) mice are functional, but, in the absence of immunization, circulating anti-Sm Ab levels are not different from those of non-Tg mice. In this report, we compare the regulation of anti-Sm B cells in nonautoimmune and autoimmune MRL/Mp-lpr/lpr (MRL/lpr) and bcl-2-22-Tg mice. Activation markers are elevated on splenic and peritoneal anti-Sm B cells of both nonautoimmune and autoimmune genetic backgrounds indicating Ag encounter. Although tolerance to Sm is maintained in 2-12H/bcl-2-22-Tg mice, it is lost in 2-12H-Tg MRL/lpr mice, as the transgene accelerates and increases the prevalence of the anti-Sm response. The 2-12H-Tg MRL/lpr mice have transitional anti-Sm B cells in the spleen similar to nonautoimmune mice. However, in contrast to nonautoimmune mice, there are few if any peritoneal anti-Sm B-1 cells. These data suggest that a defect in B-1 differentiation may be a factor in the loss of tolerance to Sm and provide insight into the low prevalence of the anti-Sm response in lupus.
Santulli-Marotto
S
S
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Qian
Y
Y
Ferguson
S
S
Clarke
S H
SH
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology; D019254:Genes, bcl-2 / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D010537:Peritoneum / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D055517:snRNP Core Proteins
D000944:Antigens, Differentiation, B-Lymphocyte; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D007143:Immunoglobulin Heavy Chains; D017411:Ribonucleoproteins, Small Nuclear; C526416:Snrpb protein, mouse; D055517:snRNP Core Proteins