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 media ted 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 deve lopment of chronic colitis. To investigate the direct role of B cells in th e suppression of this colitis, cell transfer studies were performed in TCR alpha(-/-) x 1g mu(-/-)(alpha mu(-/-)) double-mice after the adoptive knock out mice. The chronic colitis was markedly attenuated in alpha mu(-/-) tran sfer of peripheral B cells from TCR alpha(-/-) mice into 3- to 4-week-old a lpha mu(-/-) mice prior to the development of colitis. Furthermore, transfe r of mature B cells from TCR alpha(-/-) mice markedly alpha mu(-/-) mice wi th 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 n ot B7-1 (CD80). These results indicate that mature B cells play an importan t role in the development of chronic colitis in TCR alpha(-/-) mice by dire ctly regulating the pathogenic T cells (CD4(+) TCR alpha(-)beta(+) T cells) .