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B lymphocyte antigenic surveillance ...

Velazquez, Peter.

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B lymphocyte antigenic surveillance and immunoregulation in the gut mucosa: Implications for modulation of intestinal inflammation and infectious disease protection.

Record Type:	Electronic resources : Monograph/item
Title/Author:	B lymphocyte antigenic surveillance and immunoregulation in the gut mucosa: Implications for modulation of intestinal inflammation and infectious disease protection./
Author:	Velazquez, Peter.
Description:	113 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5891.
Contained By:	Dissertation Abstracts International66-11B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3196313
ISBN:	9780542422607

B lymphocyte antigenic surveillance and immunoregulation in the gut mucosa: Implications for modulation of intestinal inflammation and infectious disease protection.
Velazquez, Peter.

B lymphocyte antigenic surveillance and immunoregulation in the gut mucosa: Implications for modulation of intestinal inflammation and infectious disease protection. - 113 p.

Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5891.

Thesis (Ph.D.)--University of California, Los Angeles, 2005.

The mucosal immune system is critical for gastrointestinal homeostasis and protection from infectious organisms. B cells are key to these functions, through their well-known role in secretory IgA formation, and through their protective immunoregulatory role. In these studies, we test a panel of genetic and antigenic systems to assess the relationship of the different mucosal B cell compartments. Technologically, a simple method permits rapid and quantitative recovery of the ILF B cell compartment. Additionally, distribution and phenotype of small and large intestinal ILF B cells are further defined. A detailed analysis of the antigen sensing systems required for ILF B cell formation reveal several key findings. First, formation of the small intestinal ILF B cell population requires efficient B cell receptor (BCR)-dependent tonic signaling. Thus, mice bearing genotypes which derange BCR mediated signal (BTKxid, Galphai2) are deficient in small intestinal ILFs, while requirement for large intestinal ILFs vary. Interestingly, in a genotype that dictates irrelevant antigenic specificity muMT-/-:MD4), ILFs are not deficient in either small and large intestine. Further genetic analysis of antigenic sensing systems required for ILF B cell formation unravel a surprising molecular mechanism. Genetic deficiency of toll-like receptor (TLR) 2 or TLR4 did not impair ILF B cell formation. Similarly, the absence of TLR signaling molecules, MyD88 and TRIF, had no effect on their development. Null mutations resulting in interferon non-responsiveness, interferon-regulatory factor-3 (IRF3) and IFN-alpha receptor (IFNAR), also preserved ILF B cell formation. A striking finding is that deficiency in the non-classical class I MHC molecule, CD1d, profoundly reduced ILF but not peyer's patch (PP) B cell formation in the small intestine. Additionally, deficiency in the invariant NKT-cells, Jalpha18, results in a phenocopy of the CD1d deficiency. These data demonstrate a specific requirement for the CD1d : invariant Jalpha18 NKT-cell axis in ILF B cell formation. These findings demonstrate that BCR independent mediated sensing of the enteric microenvironment differentially regulates the stable colonization of B cells in these effector mucosal compartments. We hypothesize that CD1d ligands, either products of the enteric microbiota or the epithelial compartment, and NKT cell interaction, shape IgA-mediated bacterial surveillance in the small intestine. In the final study, the role of immunoregulatory B cells in mucosal inflammation are reported. Mesenteric lymph node (MLN) B cells protect mice from colitis induced by Galphai2 -/- CD4+ T cells. Protection required the transfer of both B cell and CD8alpha+ T cells; neither cell type alone was sufficient to inhibit CD4+ T cell-mediated colitis. Immunoregulation was associated with localization of B cells and expansion of CD4-CD8 - NKT cells in the secondary lymphoid compartment, and expansion of CD4- CD8+ T cells in the intestinal intraepithelial compartment. MLN B cells from Galphai2-/- were deficient in a phenotypic subset, and failed to provide co-transfer colitis protection. These findings indicate that protection action of B cells is a selective trait of MLN B cells with the formation of regulatory T cells associated with mucosal immune homeostasis.

ISBN: 9780542422607Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

B lymphocyte antigenic surveillance and immunoregulation in the gut mucosa: Implications for modulation of intestinal inflammation and infectious disease protection.
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500 $a Chair: Jonathan Braun.
502 $a Thesis (Ph.D.)--University of California, Los Angeles, 2005.
520 $a The mucosal immune system is critical for gastrointestinal homeostasis and protection from infectious organisms. B cells are key to these functions, through their well-known role in secretory IgA formation, and through their protective immunoregulatory role. In these studies, we test a panel of genetic and antigenic systems to assess the relationship of the different mucosal B cell compartments. Technologically, a simple method permits rapid and quantitative recovery of the ILF B cell compartment. Additionally, distribution and phenotype of small and large intestinal ILF B cells are further defined. A detailed analysis of the antigen sensing systems required for ILF B cell formation reveal several key findings. First, formation of the small intestinal ILF B cell population requires efficient B cell receptor (BCR)-dependent tonic signaling. Thus, mice bearing genotypes which derange BCR mediated signal (BTKxid, Galphai2) are deficient in small intestinal ILFs, while requirement for large intestinal ILFs vary. Interestingly, in a genotype that dictates irrelevant antigenic specificity muMT-/-:MD4), ILFs are not deficient in either small and large intestine. Further genetic analysis of antigenic sensing systems required for ILF B cell formation unravel a surprising molecular mechanism. Genetic deficiency of toll-like receptor (TLR) 2 or TLR4 did not impair ILF B cell formation. Similarly, the absence of TLR signaling molecules, MyD88 and TRIF, had no effect on their development. Null mutations resulting in interferon non-responsiveness, interferon-regulatory factor-3 (IRF3) and IFN-alpha receptor (IFNAR), also preserved ILF B cell formation. A striking finding is that deficiency in the non-classical class I MHC molecule, CD1d, profoundly reduced ILF but not peyer's patch (PP) B cell formation in the small intestine. Additionally, deficiency in the invariant NKT-cells, Jalpha18, results in a phenocopy of the CD1d deficiency. These data demonstrate a specific requirement for the CD1d : invariant Jalpha18 NKT-cell axis in ILF B cell formation. These findings demonstrate that BCR independent mediated sensing of the enteric microenvironment differentially regulates the stable colonization of B cells in these effector mucosal compartments. We hypothesize that CD1d ligands, either products of the enteric microbiota or the epithelial compartment, and NKT cell interaction, shape IgA-mediated bacterial surveillance in the small intestine. In the final study, the role of immunoregulatory B cells in mucosal inflammation are reported. Mesenteric lymph node (MLN) B cells protect mice from colitis induced by Galphai2 -/- CD4+ T cells. Protection required the transfer of both B cell and CD8alpha+ T cells; neither cell type alone was sufficient to inhibit CD4+ T cell-mediated colitis. Immunoregulation was associated with localization of B cells and expansion of CD4-CD8 - NKT cells in the secondary lymphoid compartment, and expansion of CD4- CD8+ T cells in the intestinal intraepithelial compartment. MLN B cells from Galphai2-/- were deficient in a phenotypic subset, and failed to provide co-transfer colitis protection. These findings indicate that protection action of B cells is a selective trait of MLN B cells with the formation of regulatory T cells associated with mucosal immune homeostasis.
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