Deletion and editing of B cells that express antibodies to DNA

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

Research output: Contribution to journalArticle

144 Citations (Scopus)

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

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B-Lymphocytes
Antibodies
DNA
Genes
Transgenes
Autoantibodies
Transgenic Mice
Genetic Recombination
Arginine
Spleen
Light

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Chen, C., Radic, M., 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.

Deletion and editing of B cells that express antibodies to DNA. / Chen, Ching; Radic, Marko; Erikson, Jan; Camper, Sally A.; Litwin, Samuel; Hardy, Richard R.; Weigert, Martin.

In: Journal of Immunology, Vol. 152, No. 4, 15.02.1994, p. 1970-1982.

Research output: Contribution to journalArticle

Chen, C, Radic, M, Erikson, J, Camper, SA, Litwin, S, Hardy, RR & Weigert, M 1994, 'Deletion and editing of B cells that express antibodies to DNA', Journal of Immunology, vol. 152, no. 4, pp. 1970-1982.
Chen C, Radic M, Erikson J, Camper SA, Litwin S, Hardy RR et al. Deletion and editing of B cells that express antibodies to DNA. Journal of Immunology. 1994 Feb 15;152(4):1970-1982.
Chen, Ching ; Radic, Marko ; Erikson, Jan ; Camper, Sally A. ; Litwin, Samuel ; Hardy, Richard R. ; Weigert, Martin. / Deletion and editing of B cells that express antibodies to DNA. In: Journal of Immunology. 1994 ; Vol. 152, No. 4. pp. 1970-1982.
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