Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells

Nat Immunol. 2002 May;3(5):443-50. doi: 10.1038/ni793. Epub 2002 Apr 22.

Abstract

RBP-J is a key mediator of Notch signaling that regulates cell fate determination in various lineages. To investigate the function of Notch-RBP-J in mature B cell differentiation, we generated mice that selectively lacked B cell RBP-J expression using conditional mutagenesis. Absence of RBP-J led to the loss of marginal zone B (MZB) cells with a concomitant increase in follicular B cells; in contrast, B1 cells in the peritoneal cavity were unaffected. Lack of RBP-J caused no defects in B cells maintenance, survival, plasma cell differentiation or activation. It is therefore likely that Notch-RBP-J signaling regulates the lineage commitment of mature B cells into follicular versus MZB cells. In addition, in mice with RBP-J-deficient B cells, had no obvious changes in immunoglobulin production in response to Ficoll, lipopolysaccharide or chicken gammaglobulin. In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • DNA-Binding Proteins / immunology*
  • Flow Cytometry
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Immunoglobulins / analysis
  • Immunoglobulins / biosynthesis
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Knockout
  • Mutagenesis, Insertional
  • Nuclear Proteins*
  • Receptors, Complement 3d / analysis
  • Receptors, Complement 3d / biosynthesis
  • Receptors, IgE / analysis
  • Receptors, IgE / biosynthesis
  • Receptors, Notch
  • Signal Transduction / immunology*
  • Specific Pathogen-Free Organisms
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / mortality

Substances

  • DNA-Binding Proteins
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Immunoglobulins
  • Membrane Proteins
  • Nuclear Proteins
  • Rbpj protein, mouse
  • Receptors, Complement 3d
  • Receptors, IgE
  • Receptors, Notch