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PMID: 9362534 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice.

The Journal of experimental medicine ·Vol. 186 ·No. 10 ·1997-11-17 ·Pages 1749-56

Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK

Abstract

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.

MeSH Terms
Adoptive Transfer Animals Autoantibodies/physiology Autoantigens/biosynthesis,blood B-Lymphocyte Subsets/immunology,pathology Chronic Disease Colitis/genetics,immunology,pathology,prevention & control Genes, RAG-1/immunology Immune Tolerance Immunoglobulin Heavy Chains/genetics Immunoglobulin mu-Chains/genetics Lymphocyte Transfusion Mice Mice, Inbred C57BL Mice, Knockout Receptors, Antigen, T-Cell, alpha-beta/genetics
Chemicals
Autoantibodies Autoantigens Immunoglobulin Heavy Chains Immunoglobulin mu-Chains Receptors, Antigen, T-Cell, alpha-beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mizoguchi A
Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Mizoguchi E
Smith R N
Preffer F I
Bhan A K
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.186.10.1749
Published
1997-11-17
Pages
1749-56
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2199135
Subset
IM
Grants
NIDDK NIH HHS · DK43551 · United States
NIDDK NIH HHS · DK47677 · United States
External Links
PubMed source DOI: 10.1084/jem.186.10.1749 PMC Full Text View journal details
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