Editing and escape from editing in anti-DNA B cells

Salar N. Khan, Esther J. Witsch, Noah G. Goodman, Anil K. Panigrahi, Ching Chen, Yufei Jiang, Amy M. Cline, Jan Erikson, Martin Weigert*, Eline T. Luning Prak, Marko Radic

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Tolerance to dsDNA is achieved through editing of Ig receptors that react with dsDNA. Nevertheless, some B cells with anti-dsDNA receptors escape editing and migrate to the spleen. Certain anti-dsDNA B cells that are recovered as hybridomas from the spleens of anti-dsDNA H chain transgenic mice also bind an additional, Golgi-associated antigen. B cells that bind this antigen accumulate intracellular IgM. The intracellular accumulation of IgM is incomplete, because IgM clusters are observed at the cell surface. In the spleen, B cells that express the heavy and light chains encoding this IgM are surface IgM-bright and acquire the CD21-high/CD23-low phenotype of marginal zone B cells. Our data imply that expression of an Ig that binds dsDNA and an additional antigen expressed in the secretory compartment renders B cells resistant to central tolerance. In the periphery, these B cells may be sequestered in the splenic marginal zone.

Original languageEnglish (US)
Pages (from-to)3861-3866
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number10
DOIs
StatePublished - Mar 25 2008

Keywords

  • Autoantibodies
  • B cell development
  • Receptor editing

ASJC Scopus subject areas

  • General

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    Khan, S. N., Witsch, E. J., Goodman, N. G., Panigrahi, A. K., Chen, C., Jiang, Y., Cline, A. M., Erikson, J., Weigert, M., Luning Prak, E. T., & Radic, M. (2008). Editing and escape from editing in anti-DNA B cells. Proceedings of the National Academy of Sciences of the United States of America, 105(10), 3861-3866. https://doi.org/10.1073/pnas.0800025105