B cell genotype determines the fine specificity of autoantibody in lpr mice.
Anti-Sm Abs are specific markers of human systemic lupus erythematosus (SLE) and of murine models of this disease. In humans, anti-Sm Abs are mostly IgG1, and in MRL/lpr mice, IgG2a; both are T-dependent isotypes. Other lpr strains, such as B6/lpr, do not produce anti-Sm Ab spontaneously. The present study was aimed at identifying the cellular expression of background genes responsible for generation of the anti-Sm Ab response in MRL/lpr mice. We used double chimeric mice made by transferring MRL/lpr and B6/lpr bone marrows into irradiated allotype heterozygous F1 mice. Five mo after reconstitution, FACS analysis of lymph node (LN) and spleen cells revealed that both MRL/lpr and B6/lpr cells coexisted in roughly equal numbers. Ab produced by each donor could be distinguished by allotype-specific assays. IgG2a anti-Sm was made only by MRL-derived B cells despite the presence of T cells that might potentially provide help to the B6/lpr B cells. The frequency of anti-Sm Ab-producing individuals was similar to that of unmanipulated MRL/lpr mice (about 25%). IgG2a anti-chromatin and total IgG2a was mostly dominated by the MRL-derived B cells. B6-derived B cells produced more rheumatoid factor (RF) against their own IgG2b(b), while RF against IgG2a was dominated by MRL-derived B cells. This suggests that the control of the production of particular autoantibody specificities, such as anti-Sm, is determined by the expression of MRL or B6 background genes in B cells.
Kakkanaiah
V N
VN
Department of Medicine, University of North Carolina at Chapel Hill, 27599, USA.
Sobel
E S
ES
MacDonald
G C
GC
Cheek
R L
RL
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies