T cell tolerance to germline-encoded antibody sequences in a lupus-prone mouse.
The BCR V region has been implicated as a potential avenue of T cell help for autoreactive B cells in systemic lupus erythematosus. In principle, either germline-encoded or somatically generated sequences could function as targets of such help. Preceding studies have indicated that class II MHC-restricted T cells in normal mice attain a state tolerance to germline-encoded Ab diversity. In this study, we tested whether this tolerance is intact in systemic lupus erythematosus-prone (New Zealand Black x SWR)F1 mice (SNF1). Using a hybridoma sampling approach, we found that SNF1 T cells were tolerant to germline-encoded Ab sequences. Specifically, they were tolerant to germline-encoded sequences derived from a lupus anti-chromatin Ab that arose spontaneously in this strain. This was true both for diseased and prediseased mice. Thus, there does not appear to be a global defect in T cell tolerance to Ab V regions in this autoimmune-prone strain either before or during autoimmune disease.
Guo
Wenzhong
W
Integrated Department of Immunology, National Jewish Medical and Research Center, and University of Colorado Health Science Center, Denver, CO 80206, USA.
Smith
Diana
D
Guth
Amanda
A
Aviszus
Katja
K
Wysocki
Lawrence J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics*; D001323:Autoantibodies / Q000096:biosynthesis / Q000235:genetics*; D002843:Chromatin / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D027041:Somatic Hypermutation, Immunoglobulin; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D001323:Autoantibodies; D002843:Chromatin; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region