Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction.
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 beta-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.
Witsch
Esther J
EJ
Department of Pathology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA. ewitsch@bsd.uchicago.edu
Cao
Hong
H
Fukuyama
Hidehiro
H
Weigert
Martin
M
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D002908:Chronic Disease; D006087:Graft vs Host Reaction / Q000235:genetics / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017393:RNA Editing / Q000502:physiology*
D001323:Autoantibodies; D007147:Immunoglobulin Light Chains