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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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(A) Mice were  screened for the TCR-α and  Igμ genotypes by PCR on tail  DNA. In screening of Cα locus,  the wild-type locus and the disrupted locus represent a 195-  and a 276-bp fragment, respectively. The amplification of  membrane exon of Cμ locus  yields a 700- and a 900-bp fragment corresponding to the  wild-type locus and the disrupted locus, respectively. The  left lane indicates a molecular  weight marker (bp). (B) Splenic  cells (for detection of B cells)  and MLN cells (for detection  of T cells) from TCR-α+/−,  TCR-α−/− , Igμ−/−, and TCR-α−/− × Igμ−/− mice were analyzed by FACScan®. TCR-α−/−  × Igμ−/− mice show no mature  B cells (B220+,sIgM+) and increased percentage of T cells,  comprising CD3ε+TCR-βlow  cells (TCR-α−β+ T cells expressing TCR-β chain without  TCR-α chain on cell surface)  and CD3ε+TCR-δ+ cells.
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Figure 1: (A) Mice were screened for the TCR-α and Igμ genotypes by PCR on tail DNA. In screening of Cα locus, the wild-type locus and the disrupted locus represent a 195- and a 276-bp fragment, respectively. The amplification of membrane exon of Cμ locus yields a 700- and a 900-bp fragment corresponding to the wild-type locus and the disrupted locus, respectively. The left lane indicates a molecular weight marker (bp). (B) Splenic cells (for detection of B cells) and MLN cells (for detection of T cells) from TCR-α+/−, TCR-α−/− , Igμ−/−, and TCR-α−/− × Igμ−/− mice were analyzed by FACScan®. TCR-α−/− × Igμ−/− mice show no mature B cells (B220+,sIgM+) and increased percentage of T cells, comprising CD3ε+TCR-βlow cells (TCR-α−β+ T cells expressing TCR-β chain without TCR-α chain on cell surface) and CD3ε+TCR-δ+ cells.

Mentions: As in UC patients, autoAbs such as ANCA and antitropomyosin are frequently detectable in TCR-α−/− mice (16, 25, 26), and B cells have been suspected to play a role in the pathogenesis of colitis in these mice (7, 8, 17). Therefore, to test the role of B cells in the development of colitis in TCR-α−/− mice, double mutant (TCR-α−/− × Igμ−/−) mice were generated by crossing TCR-α−/− mice with Igμ−/− mice, which lack B cells. All the mice were of inbred C57BL/6 strain. TCR-α−/− × Igμ−/− mice were obtained from F3 parents and confirmed by PCR and FACScan® (Fig. 1). As shown in Fig. 1, TCR-α−/− × Igμ−/− mice, as well as Igμ−/− mice lack mature B cells (B220+, sIgM+) and contain an increased percentage of T cells. The T cells consist of TCR-γ/δ+ cells and the unique CD3+ TCR-βlow cells which express TCR-β chains in the absence of TCR-α chains on the cell surface (23, 24).


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)

(A) Mice were  screened for the TCR-α and  Igμ genotypes by PCR on tail  DNA. In screening of Cα locus,  the wild-type locus and the disrupted locus represent a 195-  and a 276-bp fragment, respectively. The amplification of  membrane exon of Cμ locus  yields a 700- and a 900-bp fragment corresponding to the  wild-type locus and the disrupted locus, respectively. The  left lane indicates a molecular  weight marker (bp). (B) Splenic  cells (for detection of B cells)  and MLN cells (for detection  of T cells) from TCR-α+/−,  TCR-α−/− , Igμ−/−, and TCR-α−/− × Igμ−/− mice were analyzed by FACScan®. TCR-α−/−  × Igμ−/− mice show no mature  B cells (B220+,sIgM+) and increased percentage of T cells,  comprising CD3ε+TCR-βlow  cells (TCR-α−β+ T cells expressing TCR-β chain without  TCR-α chain on cell surface)  and CD3ε+TCR-δ+ cells.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2199135&req=5

Figure 1: (A) Mice were screened for the TCR-α and Igμ genotypes by PCR on tail DNA. In screening of Cα locus, the wild-type locus and the disrupted locus represent a 195- and a 276-bp fragment, respectively. The amplification of membrane exon of Cμ locus yields a 700- and a 900-bp fragment corresponding to the wild-type locus and the disrupted locus, respectively. The left lane indicates a molecular weight marker (bp). (B) Splenic cells (for detection of B cells) and MLN cells (for detection of T cells) from TCR-α+/−, TCR-α−/− , Igμ−/−, and TCR-α−/− × Igμ−/− mice were analyzed by FACScan®. TCR-α−/− × Igμ−/− mice show no mature B cells (B220+,sIgM+) and increased percentage of T cells, comprising CD3ε+TCR-βlow cells (TCR-α−β+ T cells expressing TCR-β chain without TCR-α chain on cell surface) and CD3ε+TCR-δ+ cells.
Mentions: As in UC patients, autoAbs such as ANCA and antitropomyosin are frequently detectable in TCR-α−/− mice (16, 25, 26), and B cells have been suspected to play a role in the pathogenesis of colitis in these mice (7, 8, 17). Therefore, to test the role of B cells in the development of colitis in TCR-α−/− mice, double mutant (TCR-α−/− × Igμ−/−) mice were generated by crossing TCR-α−/− mice with Igμ−/− mice, which lack B cells. All the mice were of inbred C57BL/6 strain. TCR-α−/− × Igμ−/− mice were obtained from F3 parents and confirmed by PCR and FACScan® (Fig. 1). As shown in Fig. 1, TCR-α−/− × Igμ−/− mice, as well as Igμ−/− mice lack mature B cells (B220+, sIgM+) and contain an increased percentage of T cells. The T cells consist of TCR-γ/δ+ cells and the unique CD3+ TCR-βlow cells which express TCR-β chains in the absence of TCR-α chains on the cell surface (23, 24).

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