The lupus susceptibility locus Sle1 facilitates the peripheral development and selection of anti-DNA B cells through impaired receptor editing

Soog Hee Chang, Tae Joo Kim, Young Joo Kim, Yang Liu, So Youn Min, Min Jung Park, Hyun Sil Park, Sun Kyung Lee, Ki Hoan Nam, Ho Youn Kim, Chandra Mohan, Hang Rae Kim

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3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5579-5585
Number of pages7
JournalJournal of Immunology
Volume192
Issue number12
DOIs
StatePublished - Jun 15 2014

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chang, S. H., Kim, T. J., Kim, Y. J., Liu, Y., Min, S. Y., Park, M. J., Park, H. S., Lee, S. K., Nam, K. H., Kim, H. Y., Mohan, C., & Kim, H. R. (2014). The lupus susceptibility locus Sle1 facilitates the peripheral development and selection of anti-DNA B cells through impaired receptor editing. Journal of Immunology, 192(12), 5579-5585. https://doi.org/10.4049/jimmunol.1201558