Light chain contribution to specificity in anti-DNA antibodies

S. M. Ibrahim, M. Weigert, C. Basu, J. Erikson, Marko Radic

Research output: Contribution to journalArticle

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Abstract

We studied mice expressing one of two H chain transgenes. Both transgenes expressed the same 3H9 anti-DNA VDJ, but differed in their constant domains. The IgM transgene efficiently induced tolerance and selected for a subset of endogenous L chains that prevented dsDNA binding. In contrast, the IgG2b secreted-only H chain allowed expression of a broad range of L chains, most of which yielded anti-dsDNA Ab. To deduce the features of L chains that affect DNA binding, we derived hybridomas from LPS-stimulated splenic B cells from the two transgene lines and compared the V(κ) sequences of Ab they secreted. Identification of L chains with related sequences but different binding to ssDNA, dsDNA, and cardiolipin allowed us to pinpoint L chain residues that correlate with enhanced or reduced binding. Arginines at the junction of V(κ)1 or V(κ)8 regions and J(κ)1, and arginines or asparagines in CDR1 or CDR2 enhanced DNA binding. Negatively charged residues at the same positions were found to interfere with binding. Thus, we predict that appropriate amino acids at these positions may form contacts with DNA. The likely locations of contact residues in the combining site were evaluated by inspection of previously determined Ab structures. Our results indicate that L chains in anti-DNA Ab are able to modulate DNA binding and contribute contact sites for additional determinants on a complex autoantigen.

Original languageEnglish (US)
Pages (from-to)3223-3233
Number of pages11
JournalJournal of Immunology
Volume155
Issue number6
StatePublished - Jan 1 1995
Externally publishedYes

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Antinuclear Antibodies
Transgenes
Light
DNA
Arginine
Cardiolipins
Asparagine
Autoantigens
Hybridomas
Immunoglobulin M
B-Lymphocytes
Binding Sites
Amino Acids

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Ibrahim, S. M., Weigert, M., Basu, C., Erikson, J., & Radic, M. (1995). Light chain contribution to specificity in anti-DNA antibodies. Journal of Immunology, 155(6), 3223-3233.

Light chain contribution to specificity in anti-DNA antibodies. / Ibrahim, S. M.; Weigert, M.; Basu, C.; Erikson, J.; Radic, Marko.

In: Journal of Immunology, Vol. 155, No. 6, 01.01.1995, p. 3223-3233.

Research output: Contribution to journalArticle

Ibrahim, SM, Weigert, M, Basu, C, Erikson, J & Radic, M 1995, 'Light chain contribution to specificity in anti-DNA antibodies', Journal of Immunology, vol. 155, no. 6, pp. 3223-3233.
Ibrahim SM, Weigert M, Basu C, Erikson J, Radic M. Light chain contribution to specificity in anti-DNA antibodies. Journal of Immunology. 1995 Jan 1;155(6):3223-3233.
Ibrahim, S. M. ; Weigert, M. ; Basu, C. ; Erikson, J. ; Radic, Marko. / Light chain contribution to specificity in anti-DNA antibodies. In: Journal of Immunology. 1995 ; Vol. 155, No. 6. pp. 3223-3233.
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