CD19 and BAFF-R can signal to promote B-cell survival in the absence of Syk

EMBO J. 2015 Apr 1;34(7):925-39. doi: 10.15252/embj.201489732. Epub 2015 Jan 28.

Abstract

The development and function of B lymphocytes is regulated by numerous signaling pathways, some emanating from the B-cell antigen receptor (BCR). The spleen tyrosine kinase (Syk) plays a central role in the activation of the BCR, but less is known about its contribution to the survival and maintenance of mature B cells. We generated mice with an inducible and B-cell-specific deletion of the Syk gene and found that a considerable fraction of mature Syk-negative B cells can survive in the periphery for an extended time. Syk-negative B cells are defective in BCR, RP105 and CD38 signaling but still respond to an IL-4, anti-CD40, CpG or LPS stimulus. Our in vivo experiments show that Syk-deficient B cells require BAFF receptor and CD19/PI3K signaling for their long-term survival. These studies also shed a new light on the signals regulating the maintenance of the normal mature murine B-cell pool.

Keywords: BAFF receptor; B‐cell antigen receptor; CD19; Syk; mb1‐CreERT2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / immunology
  • Animals
  • Antibodies / pharmacology
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Activation Factor Receptor / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • CD40 Antigens / antagonists & inhibitors
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Knockout
  • Oligodeoxyribonucleotides / pharmacology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / immunology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology*
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Syk Kinase

Substances

  • Antibodies
  • Antigens, CD
  • Antigens, CD19
  • B-Cell Activation Factor Receptor
  • CD40 Antigens
  • CPG-oligonucleotide
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Ly78 protein, mouse
  • Membrane Glycoproteins
  • Oligodeoxyribonucleotides
  • Receptors, Antigen, B-Cell
  • Tnfrsf13c protein, mouse
  • Interleukin-4
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse
  • Cd38 protein, mouse
  • ADP-ribosyl Cyclase 1