Light chain contribution to specificity in anti-DNA antibodies

S. M. Ibrahim, M. Weigert, C. Basu, J. Erikson, M. Z. Radic*

*Corresponding author for this work
92 Citations (Scopus)


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
JournalJournal of Immunology
Issue number6
Pages (from-to)3223-3233
Number of pages11
Publication statusPublished - 1995

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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