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Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Recent reports have shown that B cells play a key role in the pathogenesis of T cell-mediated autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic mice (NOD). We have investigated the role of B lymphocytes as APCs in the generation of autoreactive T cell responses by comparing spontaneous responses to self Ags in B cell-deficient and wild-type NOD mice. We determined that B cell-deficient mice had no spontaneous responses to 65-kDa glutamate decarboxylase (GAD65), its immunodominant peptides, and the 60-kDa heat shock protein. In contrast, these Ags are able to induce proliferative responses in the splenocyte cultures of B cell-positive NOD mice. However, T cells from B-deficient mice conserved the ability to respond to nonself Ags and mitogens. The Ag-presenting function of B cells was pivotal in the autoimmune response, since the proliferation of wild-type splenocytes to GAD65 was completely inhibited by blocking the surface Ig-mediated capture of the protein Ag by B cells. Responses to immunodominant GAD65 peptides were also absent in B cell-deficient NOD mice, suggesting that B cells are crucial with regard to the diversification of the autoimmune response to various self epitopes. We believe our results represent strong evidence that B cells are required as APCs to generate pathogenic autoimmune T cell responses and provide a direct correlation between the protection from autoimmune diabetes previously reported in B cell-deficient NOD mice and the lack of anti-GAD65 and anti-heat shock protein 60 T cell responses in these mice.
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H. Noorchashm, Y. K. Lieu, N. Noorchashm, S. Y. Rostami, S. A. S. Greeley, A. Schlachterman, H. K. Song, L. E. Noto, A. M. Jevnikar, C. F. Barker, et al. I-Ag7-Mediated Antigen Presentation by B Lymphocytes Is Critical in Overcoming a Checkpoint in T Cell Tolerance to Islet {beta} Cells of Nonobese Diabetic Mice J. Immunol., July 15, 1999; 163(2): 743 - 750. [Abstract] [Full Text] [PDF]
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O. T.M. Chan, L. G. Hannum, A. M. Haberman, M. P. Madaio, and M. J. Shlomchik A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus J. Exp. Med., May 17, 1999; 189(10): 1639 - 1648. [Abstract] [Full Text] [PDF]
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 S. Kim, S. M. Liva, M. A. Dalal, M. A. Verity, and R. R. Voskuhl Estriol ameliorates autoimmune demyelinating disease: Implications for multiple sclerosis Neurology, April 1, 1999; 52(6): 1230 - 1230. [Abstract] [Full Text] [PDF]
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B. Balasa, J. D. Davies, J. Lee, A. Good, B. T. Yeung, and N. Sarvetnick IL-10 Impacts Autoimmune Diabetes Via a CD8+ T Cell Pathway Circumventing the Requirement for CD4+ T and B Lymphocytes J. Immunol., October 15, 1998; 161(8): 4420 - 4427. [Abstract] [Full Text] [PDF]
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