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

EJ Witsch, H Cao, H Fukuyama… - The Journal of …, 2006 - rupress.org
EJ Witsch, H Cao, H Fukuyama, M Weigert
The Journal of experimental medicine, 2006rupress.org
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 β-galactosidase. This polyreactivity was …
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 β-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 κ and λ L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.
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