Sm and DNA Binding by dual reactive B cells requires distinct V{sub H}, V{sub {kappa}}, and V{sub H} CDR3 structures
- Univ. of North Carolina, Chapel Hill, NC (United States); and others
We have previously demonstrated an overlap of the anti-Sm and anti-DNA responses in MRL/Mp-Ipr/Ipr mice. The Ab produced by many anti-Sm hybridomas bind DNA and are encoded by Ig V genes used by anti-DNA hybridomas. In addition, some anti-Sm Ab that bind DNA have acquired mutations that improve DNA binding, indicating that DNA is a selecting Ag in the anti-Sm response. To gain insight into the basis for the dual binding ability of these Ab, we coexpressed the H chain from the anti-Sm hybridoma 2-12 with nine different L chains. Hybridoma 2-12 binds Sm but not DNA, yet expresses the same J558 V{sub H} gene as three anti-Sm hybridomas that bind ssDNA and at least one anti-DNA hybridoma that does not bind Sm. We found that most of the transfectoma Ab bind Sm, but their avidities vary over more than 3 orders of magnitude. Five of the nine transfectoma Ab bind ssDNA, and none bind dsDNA. In general, the ability to bind each Ag follows the binding ability of the hybridoma from which the L chain is derived. H Chain swapping experiments indicate that the H chain, V{sub H} CDR3 in particular contributes to the binding of both Sm and DNA. We conclude that Sm and DNA select for distinct features of V{sub H}, V{sub {kappa}}, and V{sub H} CDR3, suggesting selection by both Ag in the anti-Sm response.
- OSTI ID:
- 160158
- Journal Information:
- Journal of Immunology, Vol. 155, Issue 4; Other Information: PBD: 15 Aug 1995
- Country of Publication:
- United States
- Language:
- English
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