Deletion and editing of B cells that express antibodies to DNA

Ching Chen, Marko Z. Radic, Jan Erikson, Sally A. Camper, Samuel Litwin, Richard R. Hardy, Martin Weigert*

*Corresponding author for this work

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

We previously demonstrated that in mice 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 κ light chain genes to generate a non-dsDNA-binding Ab; and 3) expression of a rare Vλ gene, Vλx, to generate a non-DNA-binding Ab.

Original languageEnglish (US)
Pages (from-to)1970-1982
Number of pages13
JournalJournal of Immunology
Volume152
Issue number4
StatePublished - Feb 15 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chen, C., Radic, M. Z., Erikson, J., Camper, S. A., Litwin, S., Hardy, R. R., & Weigert, M. (1994). Deletion and editing of B cells that express antibodies to DNA. Journal of Immunology, 152(4), 1970-1982.