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

• Published in: The Journal of experimental medicine Vol. 171; no. 2; pp. 503 - 517
• Main Authors: MORRIS, S. C, CHEEK, R. L, COHEN, P. L, EISENBERG, R. A
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.02.1990; The Rockefeller University Press
• Subjects: Animals; Autoantibodies - immunology; B-Lymphocytes - immunology; Biological and medical sciences; Cell Communication; Chimera; Chromatin - immunology; Enzyme-Linked Immunosorbent Assay; Erythrocytes - immunology; Female; Graft vs Host Disease - immunology; Immunoglobulin Allotypes - immunology; Immunoglobulin G - analysis; Immunoglobulin M - analysis; Immunopathology; Medical sciences; Mice; Mice, Inbred C57BL - genetics; T-Lymphocytes - immunology; Immunopathology; Animal model; Animal; Interaction; Autoantibody; Exploration; Graft versus host reaction
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.171.2.503

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.