Affiliation:
1. From the Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114
Abstract
The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-α−/− mice was explored by creating double mutant mice (TCR-α−/− × immunoglobulin (Ig)μ−/−), which lack B cells. TCR-α−/− × Igμ−/− mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-α−/− mice. Colitis was induced in recombination-activating gene-1 (RAG-1−/−) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-α−/− × Igμ−/− mice. When purified B cells from TCR-α−/− mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1−/− mice. Administration of the purified Ig from TCR-α−/− mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-α−/− × Igμ−/− mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-α−/− × Igμ−/− mice as compared to Igμ−/− mice and TCR-α−/− mice. Administration of the purified Ig from TCR-α−/− mice into TCR-α−/− × Igμ−/− mice led to decrease in the number of apoptotic cells. These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Reference44 articles.
1. Myasthenia gravis;Lindstrom;Adv Immunol,1988
2. Oral administration of lipopolysaccharides activates B-1 cells in peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse;Murakami;J Exp Med,1994
3. Broken dogma: penetration of autoantibodies into living cells;Alarcon-Segovia;Immunol Today,1995
4. Inflammatory bowel disease I;Podolsky;N Engl J Med,1991
5. Autoimmunity to cytoskeletal protein tropomyosin: a clue to the pathogenic mechanisms for ulcerative colitis;Das;J Immunol,1993
Cited by
294 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献