Autoantibodies in chronic graft versus host result from cognate T-B interactions

doi:10.1084/jem.171.2.503

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Autoantibodies in chronic graft versus host result from cognate T-B interactions

SC Morris, RL Cheek, PL Cohen and RA Eisenberg
Department of Microbiology/Immunology, University of North Carolina, Chapel Hill 27599.

A chronic graft-versus-host reaction (GVH) induced in nonautoimmune mice causes a syndrome that closely resembles SLE. In this model, donor T cells react against incompatible host Ia structures and generate excessive help, which activates a subpopulation of self-reactive B cells. We have studied whether these self-reactive B cells are activated by direct interaction with alloreactive T cells or by nonspecific bystander effects. Two types of chimeras were made: double- parental chimeras, differing at both Ia and Igh allotype [B6.C20 + bm12- ---(B6.C20 x bm12)F1]; and control chimeras [(B6.C20 x bm12)F1---- (B6.C20 x bm12)F1]. A chronic GVH syndrome was induced in the chimeras by infusion of B6 or bm12 spleen cells. Coombs and antichromatin autoantibodies were measured using Igh allotype-specific immunoassays. The double-parental chimeras that received bm12 cells made autoantibodies principally of the Igha allotype, indicating that the bm12 T cells interacted only with the Iab-bearing host B cells. Conversely, double-parental chimeras that received B6 cells made mostly Ighb autoantibodies, indicating direct cognate interaction with the Iabm12-bearing host B cells. The control chimeras made autoantibodies of both allotypes. These results indicate that autoantibodies in chronic GVH result from direct T-B interactions and not from nonspecific T cell-derived factors.
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