Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice

The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR-alpha(-/-) mice was explored by creating double mutant mice (TCR-alpha(-/-) X immunoglobulin (Ig)mu(-/-)), which lack B cells. TCR-alpha(-/-) X Ig mu(-/-) mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-alpha(-/-) mice. Colitis was induced in recombination-activating gene-1 (RAG-1(-/-)) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-alpha(-/-) X Ig mu(-/-) mice. When purified B cells from TCR-alpha(-/-) mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1(-/-) mice. Administration of the purified Ig from TCR-alpha(-/-) mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha(-/-) X Ig mu (-/-) mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-alpha(-/-) X Ig mu(-/-) mice as compared to Ig mu(-/-) mice and TCR-alpha(-/-) mice. Administration of the purified Ig from TCR-alpha(-/-) mice into TCR-alpha(-/-) X Ig mu(-/-) 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.