Abstract
MZ B cells represent a distinct lineage of naive B lymphocytes, apart from FO B cells and peritoneal B1 cells, and mediate humoral immune responses against blood-borne type 2 T-independent antigens. Regulation of MZ B cell development involves the Notch receptor signaling, the intensity of B cell receptor signals, and cell compartmentalization by adhesion and chemokine receptors. Our previous work showed that gene-targeted mice expressing a truncated form of the putative signaling adapter protein SLy1 exhibit reduced numbers of a splenic B cell population enriched in MZ B cells. Here, we demonstrate that Sly1(d/d) mice exhibit a partial, but selective, block in the transition from pre-MZ to mature MZ B cells. Development of both T1 and T2 precursor subsets and FO B cells was normal in Sly1(d/d) mice. Consistent with the loss of MZ B cells, the production of antigen-specific IgM antibodies following immunization with pneumococcal polysaccharides was severely impaired in Sly1(d/d) mice. Importantly, expression of the Notch signaling mediator RBP-J and the Notch target genes Hes-1 and Hes-5 was markedly reduced in MZ but not FO B cells of Sly1(d/d) mice. In contrast, B cell receptor signaling, expression and function of LFA-1 and alpha4-integrins, and expression of chemokine receptors appeared intact in Sly1(d/d) cells. Collectively, these results provide strong evidence that SLy1 is important for the generation and function of MZ B cells and suggest a novel link between SLy1 and the activity of the Notch pathway in the development of MZ B cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport
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Animals
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Antibody Formation / genetics
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Antibody Formation / immunology
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B-Lymphocytes / immunology*
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / immunology
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / immunology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / immunology
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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Immunoglobulin M / genetics
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Immunoglobulin M / immunology
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Integrin alpha4 / genetics
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Integrin alpha4 / immunology
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Lymphocyte Function-Associated Antigen-1 / genetics
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Lymphocyte Function-Associated Antigen-1 / immunology
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Mice
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Mice, Mutant Strains
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology
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Receptors, Notch / genetics
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Receptors, Notch / immunology*
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Repressor Proteins / genetics
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Repressor Proteins / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Th1 Cells / immunology
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Th2 Cells / immunology
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Transcription Factor HES-1
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors
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Hes1 protein, mouse
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Hes5 protein, mouse
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Homeodomain Proteins
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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Immunoglobulin M
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Lymphocyte Function-Associated Antigen-1
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Rbpj protein, mouse
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Receptors, Antigen, B-Cell
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Receptors, Notch
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Repressor Proteins
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SLY1 protein, mouse
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Transcription Factor HES-1
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Integrin alpha4