TY - JOUR
T1 - Genetic Dissection of Systemic Lupus Erythematosu Pathogenesis
T2 - Sle2 on Murine Chromosome 4 Leads to B Cell Hyperactivity
AU - Mohan, Chandra
AU - Morel, Laurence
AU - Yang, Ping
AU - Wakeland, Edward K.
N1 - Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.
PY - 1997
Y1 - 1997
N2 - Susceptibility to systemic lupus erythematosus in the NZM2410 murine model maps to Sle1, Sle2, Sle3, and the H2 loci. To unravel how these loci contribute to the pathogenesis of lupus, individual NZM2410-derived genomic intervals bearing these loci have been successfully backcrossed onto the resistant C57BL/6 (B6) background. The focus of this study was to understand how Sle2 on murine chromosome 4 impacts the immune system. Compared with C57BL/6 (B6) mice, B6 mice congenic for Sle2 exhibit a variety of immunophenotypes affecting their B cells. They have an early, but transient, expansion of splenic, CD23low B cells. Thereafter, their B cells appear activated by surface phenotype and functional criteria, paralleled by elevated serum levels of polyreactive/polyclonal IgM. Importantly, Sle2 leads to a heightened B cell responsiveness to in vitro stimuli and to in vivo antigenic challenge. Finally, they exhibit increased levels of peritoneal and splenic B1 cells. Thus, Sle2 harbors a gene that leads to B cell hyperactivity and elevated B1 cell formation. However, Sle2 by itself on the normal B6 background is insufficient to generate IgG antinuclear Abs (ANA) or nephritis. By reducing the B cell signaling threshold, Sle2 might serve to amplify an ongoing autolmmune response.
AB - Susceptibility to systemic lupus erythematosus in the NZM2410 murine model maps to Sle1, Sle2, Sle3, and the H2 loci. To unravel how these loci contribute to the pathogenesis of lupus, individual NZM2410-derived genomic intervals bearing these loci have been successfully backcrossed onto the resistant C57BL/6 (B6) background. The focus of this study was to understand how Sle2 on murine chromosome 4 impacts the immune system. Compared with C57BL/6 (B6) mice, B6 mice congenic for Sle2 exhibit a variety of immunophenotypes affecting their B cells. They have an early, but transient, expansion of splenic, CD23low B cells. Thereafter, their B cells appear activated by surface phenotype and functional criteria, paralleled by elevated serum levels of polyreactive/polyclonal IgM. Importantly, Sle2 leads to a heightened B cell responsiveness to in vitro stimuli and to in vivo antigenic challenge. Finally, they exhibit increased levels of peritoneal and splenic B1 cells. Thus, Sle2 harbors a gene that leads to B cell hyperactivity and elevated B1 cell formation. However, Sle2 by itself on the normal B6 background is insufficient to generate IgG antinuclear Abs (ANA) or nephritis. By reducing the B cell signaling threshold, Sle2 might serve to amplify an ongoing autolmmune response.
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M3 - Article
C2 - 9200486
AN - SCOPUS:0031179651
SN - 0022-1767
VL - 159
SP - 454
EP - 465
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -