| Author |
Park, Min-Jung Park, Hyun-Sil Kim, Young-Joo Nam, Ki-Hoan Kim, Ho-Youn Lee, Sun-Kyung Mohan, Chandra Chang, Soog-Hee Liu, Yang Kim, Hang-Rae Min, So-Youn Kim, Tae-Joo |
| Description |
Author Affiliation: Chang SH ( Department of Anatomy and Biomedical Sciences, Seoul National University College of Medicine, Jongno-gu, Seoul 110-799, Republic of Korea); Kim TJ ( Department of Anatomy and Biomedical Sciences, Seoul National University College of Medicine, Jongno-gu, Seoul 110-799, Republic of Korea); Kim YJ ( Department of Anatomy and Biomedical Sciences, Seoul National University College of Medicine, Jongno-gu, Seoul 110-799, Republic of Korea); Liu Y ( Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390); Min SY ( Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390); Park MJ ( Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seocho-Gu, Seoul, 137-040, Republic of Korea); Park HS ( Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seocho-Gu, Seoul, 137-040, Republic of Korea); Lee SK ( Department of Anatomy and Biomedical Sciences, Seoul National University College of Medicine, Jongno-gu, Seoul 110-799, Republic of Korea); Nam KH ( Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.); Kim HY ( Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seocho-Gu, Seoul, 137-040, Republic of Korea); Mohan C ( Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390); Kim HR ( Department of Anatomy and Biomedical Sciences, Seoul National University College of Medicine, Jongno-gu, Seoul 110-799, Republic of Korea) |
| Abstract |
Systemic lupus erythematosus is characterized by the spontaneous production of IgG autoantibodies in patients and lupus-prone mice. In this study, we investigated the effect of the Sle1 lupus susceptibility locus on the peripheral development of 56R(+) anti-DNA transgenic B cells by tracking 56R(+) B cells in mice without (B6.56R) or with (B6.Sle1.56R) the Sle1 locus. Compared with B6.56R mice, B6.Sle1.56R mice exhibited increased class-switched IgG2a anti-DNA Abs in their serum, encoded by the transgene. Interestingly, within the spleen, Sle1 facilitated the development of these cells into clusters of IgG2a class-switched B cells juxtaposed to CD4(+) T cells within extrafollicular sites. Through sequence analysis of B cell hybridomas, we also found that B cells from B6.Sle1.56R mice are inefficient at Ig H and L chain editing. Thus, the Ig H chains in Sle1.56R(+) B cells are partnered more often with cationic L chains that facilitate DNA binding. Taken together, these findings indicate that the Sle1 lupus-susceptibility locus may facilitate the emergence of anti-DNA B cells by subduing BCR revision and possibly by shaping the extrafollicular development of effector B cells, although the precise molecular mechanisms await further study. |
