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The Journal of Immunology, 2006, 176: 6879-6887.
Copyright © 2006 by The American Association of Immunologists

Development and Selection of Edited B Cells in B6.56R Mice1

Debora R. Sekiguchi*, Lenka Yunk*, David Gary{dagger}, Deepshikha Charan*, Bhaskar Srivastava*, David Allman*, Martin G. Weigert{dagger} and Eline T. Luning Prak2,*

* Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and {dagger} Gwen Knapp Center for Lupus and Autoimmunity Research, University of Chicago, Chicago, IL 60637

Tolerance to dsDNA is broken in mice with a high-affinity anti-DNA H chain transgene, 56R, on the C57BL/6 background (B6.56R). B6.56R produce more anti-dsDNA Abs than BALBc.56R. To investigate how anti-DNA Abs are regulated on the B6 background, phenotypic and genetic studies were performed. B6.56R have reduced numbers of B cells and phenotypically altered B cell subsets, including relative increases in the proportions of IgM-negative bone marrow B cells, cells with a marginal zone phenotype, and cells with a transitional T3 phenotype. The peripheral B cell repertoire in B6.56R is restricted: most B cells express the 56R H chain and use a similar, limited subset of editor L chains. DNA binding is more common in B6.56R because the repertoire is shifted toward L chains that are more permissive for DNA binding. H chain editing is also observed and is increased in spontaneous as compared with LPS hybridomas. A subset of spontaneous hybridomas appears to lack H chain expression.




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