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T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse¹

Wenzhong Guo^*, Diana Smith^*, Amanda Guth, Katja Aviszus^* and Lawrence J. Wysocki^2,*

^* Integrated Department of Immunology, National Jewish Medical and Research Center, and University of Colorado Health Science Center, Denver, CO 80206; and Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523

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.

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				A Guth, T Detanico, D Smith, K. Tung, C Bonorino, and L. Wysocki Spontaneous autoimmunity in mice that carry an IghV partial transgene: a required arginine in VHCDR3 Lupus, April 1, 2009; 18(4): 299 - 308. [Abstract] [PDF]