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Editing and escape from editing in anti-DNA B cells

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...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2008-03, Vol.105 (10), p.3861-3866
Main Authors: Khan, Salar N, Witsch, Esther J, Goodman, Noah G, Panigrahi, Anil K, Chen, Ching, Jiang, Yufei, Cline, Amy M, Erikson, Jan, Weigert, Martin, Prak, Eline T. Luning, Radic, Marko
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Language:English
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0800025105