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

The spontaneous chronic colitis in TCR a mutant (TCR alpha(-/-)) mice mediated by CD4(+) TCR alpha(-)beta(+) 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 TCR alpha(-/-) x 1g mu(-/-)(alpha mu(-/-)) double-mice after the adoptive knockout mice. The chronic colitis was markedly attenuated in alpha mu(-/-) transfer of peripheral B cells from TCR alpha(-/-) mice into 3- to 4-week-old alpha mu(-/-) mice prior to the development of colitis. Furthermore, transfer of mature B cells from TCR alpha(-/-) mice markedly alpha mu(-/-) mice with established decreased the number of pathogenic colonic CD4(+) TCR alpha(-)beta(+) T cells in alpha mu(-/-) 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 TCR alpha(-/-) mice by directly regulating the pathogenic T cells (CD4(+) TCR alpha(-)beta(+) T cells).