Reduced notch activity is associated with an impaired marginal zone B cell development and function in Sly1 mutant mice

Mol Immunol. 2009 Feb;46(5):969-77. doi: 10.1016/j.molimm.2008.09.023. Epub 2008 Oct 31.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / immunology
  • B-Lymphocytes / immunology*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / immunology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / immunology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Integrin alpha4 / genetics
  • Integrin alpha4 / immunology
  • Lymphocyte Function-Associated Antigen-1 / genetics
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Mice
  • Mice, Mutant Strains
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Notch / genetics
  • Receptors, Notch / immunology*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Transcription Factor HES-1


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Hes5 protein, mouse
  • Homeodomain Proteins
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Immunoglobulin M
  • Lymphocyte Function-Associated Antigen-1
  • Rbpj protein, mouse
  • Receptors, Antigen, B-Cell
  • Receptors, Notch
  • Repressor Proteins
  • SLY1 protein, mouse
  • Transcription Factor HES-1
  • Integrin alpha4