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Chen C , Radic MZ , Erikson J , Camper SA , Litwin S , Hardy RR , Weigert M
Deletion and Editing of B-Cells That Express Antibodies to DNA
Journal of Immunology. 1994 Feb 15;152(4) :1970-1982
PMID: ISI:A1994MY84400052   
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We previously demonstrated that in m ice transgenic for genes coding for an anti-ssDNA autoantibody B cells were functionally inactivated but not physically deleted. We have now extended this model by introducing an arginine into the CDR2 of the heavy chain transgene. This change alters the specificity of the Ab from anti-ssDNA to anti-dsDNA and increases the affinity for ssDNA. Mice carrying this transgene displayed a significant reduction of peripheral B cells and anti-dsDNA B cells were not recovered from the spleens. The remaining B cells escape deletion by revising their Ag receptors in several ways: 1) elimination of the transgenic heavy chain gene via intrachromosomal recombination, followed by rearrangement and expression of endogenous V-H genes; 2) ongoing rearrangement of endogenous kappa light chain genes to generate a non-dsDNA- binding Ab; and 3) expression of a rare V lambda gene, V lambda x, to generate a non-DNA-binding Ab.
English Article MY844 J IMMUNOL