Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice.
The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR)-alpha-/- mice was explored by creating double mutant mice (TCR-alpha-/- x immunoglobulin (Ig)mu-/-), which lack B cells. TCR-alpha-/- x Ig mu-/- mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-alpha-/- mice. Colitis was induced in recombination-activating gene-1 (RAG-1-/-) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-alpha-/- x Ig mu-/- mice. When purified B cells from TCR-alpha-/- mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1-/- mice. Administration of the purified Ig from TCR-alpha-/- mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha-/- x Ig mu-/- mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-alpha-/- x Ig mu-/- mice as compared to Ig mu-/- mice and TCR-alpha-/- mice. Administration of the purified Ig from TCR-alpha-/- mice into TCR-alpha-/- x Ig mu-/- 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.
Mizoguchi
A
A
Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Mizoguchi
E
E
Smith
R N
RN
Preffer
F I
FI
Bhan
A K
AK
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000502:physiology; D001324:Autoantigens / Q000096:biosynthesis / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D016654:Genes, RAG-1 / Q000276:immunology; D007108:Immune Tolerance; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D001323:Autoantibodies; D001324:Autoantigens; D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta