The Journal of Experimental Medicine
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Published online 26 June 2006 doi:10.1084/jem.20060075
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 7, 1761-1772
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ARTICLE

 Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction

Esther J. Witsch1, Hong Cao1, Hidehiro Fukuyama2, and Martin Weigert1

1 Department of Pathology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637 2 Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021

CORRESPONDENCE Esther Witsch: ewitsch{at}bsd.uchicago.edu

The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4+ T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and ß-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with "editor" L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress {kappa} and {lambda} L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.

Abbreviations used: Ab, antibody; Arg, arginine; Asp, aspartate; CDR, complementarity-determining region; cGvH, chronic graft-versus-host; ds, double-stranded; MBP, myelin basic protein; MZ, marginal zone; PS, phosphatidylserine.


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