Regulatory role of mature B cells in a murine model of inflammatory bowel disease

Abstract

The spontaneous chronic colitis in TCR α mutant (TCRα^–/–) mice mediated by CD4⁺ TCRα^–β⁺ T cells is more severe in the absence of mature B cells, suggesting a suppressive role of B cells and Ig in the development of chronic colitis. To investigate the direct role of B cells in the suppression of this colitis, cell transfer studies were performed in TCRα^–/– × Igμ^–/– (αμ^–/–) double-knockout mice. The chronic colitis was markedly attenuated in αμ^–/– mice after the adoptive transfer of peripheral B cells from TCRα^–/– mice into 3- to 4-week-old αμ^–/– mice prior to the development of colitis. Furthermore, transfer of mature B cells from TCRα^–/– mice markedly decreased the number of pathogenic colonic CD4⁺ TCRα^–β⁺ T cells in αμ^–/– mice with established colitis. This B cell effect required the presence of functional co-stimulatory molecules CD40 and B7-2 (CD86) but not B7-1 (CD80). These results indicate that mature B cells play an important role in the development of chronic colitis in TCRα^–/– mice by directly regulating the pathogenic T cells (CD4⁺ TCRα^–β⁺ T cells).