Influence of the Ig H chain locus on autoantibody production in autoimmune mice

M. D. Halpern, C. L. Fisher, P. L. Cohen, R. A. Eisenberg

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Autoimmune disease is influenced by multiple genes. In this study, we investigated the role of one genetic locus, Ig H chain. IgG2a antichromatin, anti-ssDNA, and antihistone autoantibodies (autoAb) from (MRL/Mp-lpr/lpr × C57BL/6-lpr/lpr), (Ighj/b); (C57BL/6-lpr/lpr × C57BL/6-lpr/lpr-Igha), (Ighb/a); and (MRL/Mp-lpr/lpr × MRL/Mp-lpr/lpr-Ighb), (Ighj/b) mice were determined using allotype-specific ELISA. Strikingly, antichromatin and antihistone antibodies (Ab) were comprised of significantly more b allotype than either a or j allotype in all cohorts of F1 mice examined. In mice that produced anti-Sm Ab, the b allotype was used preferentially for these autoAb as well. However, no allotype skewing was observed in IgG2a Ab directed against TNP or DNA, or for total IgG2a. An Igh recombinant locus was utilized to examine the genetic control of b allotype skewing in Ipr mice and in chronic graft vs host disease. In both models, the VH region did not appear to be responsible for the preferential use of b allotype. These results indicate a contribution to autoimmunity by the Igh locus and raise the possibility that Ig allotype may influence autoimmune disease by its effect on the production of certain autoAb.

Original languageEnglish (US)
Pages (from-to)3735-3740
Number of pages6
JournalJournal of Immunology
Issue number11
StatePublished - 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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