Acknowledgements The research was supported by grants from the NIH, the Arthritis Foundation, and the Lupus Foundation, and gifts from the Paxson Family Foundation, RRS is recipient of an Arthritis Investigator Award from the National Arthritis Foundation, We sincerely thank Eli Sercarz, Fanny Ebling, Kamal Moudgil, Betty Tsao and Jonathan Jacinto for their intellectual and technical contributions.
Reciprocal T-B determinant spreading develops spontaneously in murine lupus: implications for pathogenesis
Article first published online: 28 APR 2006
Volume 164, Issue 1, pages 201–203, August 1998
How to Cite
Singh, R. R. and Hahn, B. H. (1998), Reciprocal T-B determinant spreading develops spontaneously in murine lupus: implications for pathogenesis. Immunological Reviews, 164: 201–203. doi: 10.1111/j.1600-065X.1998.tb01221.x
- Issue published online: 28 APR 2006
- Article first published online: 28 APR 2006
Summary: Recent work from several laboratories has shown that, in contrast to the widely held notion that one autoimmune disease is caused by one or a few related autoantigenic determinants, autoimmunity is fundamentally a continuously evolving process. The autoimmune responses shift, drift and diversify with time not only to other determinants in the original antigen but also to other antigens. We have described a form of determinant spreading - reciprocal T-B determinant spreading–where the induction of first T cells by peptides from an autoantibody molecule could lead to help provided to a variety of B cells displaying a cross-reactive version of the original determinant. The response spreads in this way by reciprocal T-B stimulation until large cohorts of T and B cells have expanded. Such spontaneous expansion must be important in clinical disease, since tolerance induction to a limited set of T-cell determinant peptides derived from an anti-DNA antibody VH region delayed the appearance of IgG anti-dsDNA antibodies and onset of lupus nephritis in the NZB/NZW Fl mouse model of systemic lupus erythematosus. Understanding the diversification patterns in autoimmune responses has enormous implications in developing peptide-targeted therapies.