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

Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK - J. Exp. Med. (1997)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.

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.

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The severity of colitis determined by histological examinations in TCR-α−/−, Igμ−/−, and TCR-α−/− × Igμ−/− mice at 4, 8, 12,  and 20 wk of age maintained under specific pathogen-free conditions.
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Figure 3: The severity of colitis determined by histological examinations in TCR-α−/−, Igμ−/−, and TCR-α−/− × Igμ−/− mice at 4, 8, 12, and 20 wk of age maintained under specific pathogen-free conditions.

Mentions: Fig. 2 shows the gross appearance of the distal part of colons from TCR-α−/− and TCR-α−/− × Igμ−/− mice at 8 wk of age. The colons from TCR-α−/− mice have a normal beaded appearance due to the presence of firm stools in the lumen. In contrast, the colons from TCR-α−/− × Igμ−/− mice have thickened wall with presence of loose stools. Fig. 3 shows the severity of colitis in TCR-α−/−, Igμ−/−, and TCR-α−/− × Igμ−/− mice maintained under specific pathogen-free conditions. Igμ−/− mice did not develop colitis. In TCR-α−/− mice, ∼70% of mice developed colitis by 20 wk of age, whereas only 17% of mice showed evidence of colitis by 12 wk of age. In contrast, all the TCR-α−/− × Igμ−/− mice developed a more severe colitis by 8 wk of age, suggesting that the disease in TCR-α−/− × Igμ−/− mice develops faster than in TCR-α−/− mice. Since TCR-α−/− × Igμ−/− mice are more immunocompromised than TCR-α−/− mice, it is possible that the severe colitis in these mice may be related to the presence of pathogens. However, enteric pathogenic organisms were not detected in the TCR-α−/− and TCR-α−/− × Igμ−/− mice maintained under pathogen-free conditions as confirmed by the studies performed at The Charles River Laboratories (Wilmington, MA). We also orally administered (three times) cecal contents from TCR-α−/− × Igμ−/− mice with colitis into immunodeficient RAG-1−/− and SCID mice to investigate the possibility that an unknown pathogen may be present in TCR-α−/− × Igμ−/− mice. However, no colitis was recognized in these RAG-1−/− and SCID mice 8 wk after oral administration (data not shown). These findings taken together indicate that, like the other murine models of human IBD (15, 16), B cells are not necessary for the development of spontaneous colitis in TCR-α−/− mice. However, unlike other models, mature B cells or their products may have a regulatory role in the pathogenesis of this colitis in TCR-α−/− mice.


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

Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK - J. Exp. Med. (1997)

The severity of colitis determined by histological examinations in TCR-α−/−, Igμ−/−, and TCR-α−/− × Igμ−/− mice at 4, 8, 12,  and 20 wk of age maintained under specific pathogen-free conditions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199135&req=5

Figure 3: The severity of colitis determined by histological examinations in TCR-α−/−, Igμ−/−, and TCR-α−/− × Igμ−/− mice at 4, 8, 12, and 20 wk of age maintained under specific pathogen-free conditions.
Mentions: Fig. 2 shows the gross appearance of the distal part of colons from TCR-α−/− and TCR-α−/− × Igμ−/− mice at 8 wk of age. The colons from TCR-α−/− mice have a normal beaded appearance due to the presence of firm stools in the lumen. In contrast, the colons from TCR-α−/− × Igμ−/− mice have thickened wall with presence of loose stools. Fig. 3 shows the severity of colitis in TCR-α−/−, Igμ−/−, and TCR-α−/− × Igμ−/− mice maintained under specific pathogen-free conditions. Igμ−/− mice did not develop colitis. In TCR-α−/− mice, ∼70% of mice developed colitis by 20 wk of age, whereas only 17% of mice showed evidence of colitis by 12 wk of age. In contrast, all the TCR-α−/− × Igμ−/− mice developed a more severe colitis by 8 wk of age, suggesting that the disease in TCR-α−/− × Igμ−/− mice develops faster than in TCR-α−/− mice. Since TCR-α−/− × Igμ−/− mice are more immunocompromised than TCR-α−/− mice, it is possible that the severe colitis in these mice may be related to the presence of pathogens. However, enteric pathogenic organisms were not detected in the TCR-α−/− and TCR-α−/− × Igμ−/− mice maintained under pathogen-free conditions as confirmed by the studies performed at The Charles River Laboratories (Wilmington, MA). We also orally administered (three times) cecal contents from TCR-α−/− × Igμ−/− mice with colitis into immunodeficient RAG-1−/− and SCID mice to investigate the possibility that an unknown pathogen may be present in TCR-α−/− × Igμ−/− mice. However, no colitis was recognized in these RAG-1−/− and SCID mice 8 wk after oral administration (data not shown). These findings taken together indicate that, like the other murine models of human IBD (15, 16), B cells are not necessary for the development of spontaneous colitis in TCR-α−/− mice. However, unlike other models, mature B cells or their products may have a regulatory role in the pathogenesis of this colitis in TCR-α−/− mice.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Immunopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.

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.

Show MeSH
Related in: MedlinePlus