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Title | The lupus susceptibility locus Sle1 facilitates the peripheral development and selection of anti-DNA B cells through impaired receptor editing |
| Lupus 민감유전자인 Sle1이receptor editing에 손상을 초래하여 말초에서의 Anti-DNA B 세포의 발달과 선택을 촉진 |
Authors | S H Chang; T J Kim; Y J Kim; Y Liu; S Y Min; M J Park; H S Park; S K Lee; Ki Hoan Nam; H Y Kim; C Mohan; H R Kim |
Publisher | American Association of Immunologists |
Issue Date | 2014 |
Citation | Journal of Immunology, vol. 192, no. 12, pp. 5579-5585 |
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 lupussusceptibility 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. |
ISSN | 0022-1767 |
Link | |
Appears in Collections | |
Registered Date |
2017-04-19 |
