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

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(-/-) X immunoglobulin (Ig)μ(-/-)), which lack B cells. TCR-α(-/-) X 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(-/-) X 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(-/-) X Igμ(-/-) mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-α(-/-) X Igμ(-/-) mice as compared to Igμ(-/-) mice and TCR-α(-/-) mice. Administration of the purified Ig from TCR-α(-/-) mice into TCR-α(-/-) X 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.