Regulatory role of mature B cells in a murine model of inflammatory bowel disease.
The spontaneous chronic colitis in TCR alpha mutant (TCRalpha(-/-)) mice mediated by CD4(+) TCRalpha(-)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 TCRalpha(-/-) x Igmu(-/-) (alphamu(-/-)) double-knockout mice. The chronic colitis was markedly attenuated in alphamu(-/-) mice after the adoptive transfer of peripheral B cells from TCRalpha(-/-) mice into 3- to 4-week-old alphamu(-/-) mice prior to the development of colitis. Furthermore, transfer of mature B cells from TCRalpha(-/-) mice markedly decreased the number of pathogenic colonic CD4(+) TCRalpha(-)beta(+) T cells in alphamu(-/-) 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 TCRalpha(-/-) mice by directly regulating the pathogenic T cells (CD4(+) TCRalpha(-)beta(+) T cells).
Mizoguchi
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Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom Street-Cox 5, Boston, MA 02114, USA.
Mizoguchi
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A
Preffer
F I
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Bhan
A K
AK
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency; D013047:Specific Pathogen-Free Organisms
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta