B cell genotype determines the fine specificity of autoantibody in lpr mice

• Published in: The Journal of immunology (1950) Vol. 159; no. 2; pp. 1027 - 1035
• Main Authors: Kakkanaiah, VN, Sobel, ES, MacDonald, GC, Cheek, RL, Cohen, PL, Eisenberg, RA
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.1997
• Subjects: Animals; Antibody Specificity; Autoantibodies - genetics; Autoantibodies - immunology; B-Lymphocytes - immunology; Disease Models, Animal; Humans; Lupus Erythematosus, Systemic - immunology; Mice; Mice, Mutant Strains; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.159.2.1027

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.