The BAFF receptor transduces survival signals by co-opting the B cell receptor signaling pathway

Immunity. 2013 Mar 21;38(3):475-88. doi: 10.1016/j.immuni.2012.11.015. Epub 2013 Feb 28.

Abstract

Follicular B cell survival requires signaling from BAFFR, a receptor for BAFF and the B cell antigen receptor (BCR). This "tonic" BCR survival signal is distinct from that induced by antigen binding and may be ligand-independent. We show that inducible inactivation of the Syk tyrosine kinase, a key signal transducer from the BCR following antigen binding, resulted in the death of most follicular B cells because Syk-deficient cells were unable to survive in response to BAFF. Genetic rescue studies demonstrated that Syk transduces BAFFR survival signals via ERK and PI3 kinase. Surprisingly, BAFFR signaling directly induced phosphorylation of both Syk and the BCR-associated Igα signaling subunit, and this Syk phosphorylation required the BCR. We conclude that the BCR and Igα may be required for B cell survival because they function as adaptor proteins in a BAFFR signaling pathway leading to activation of Syk, demonstrating previously unrecognized crosstalk between the two receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Animals
  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / pharmacology
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Activation Factor Receptor / immunology*
  • B-Cell Activation Factor Receptor / metabolism
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD79 Antigens / immunology
  • CD79 Antigens / metabolism
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / immunology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases / immunology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / immunology
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology*
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / genetics
  • Proteins / immunology
  • Proteins / metabolism
  • RNA, Untranslated
  • Receptor Cross-Talk / immunology
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Syk Kinase
  • Tamoxifen / pharmacology

Substances

  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • CD79 Antigens
  • Gt(ROSA)26Sor non-coding RNA, mouse
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • RNA, Untranslated
  • Receptors, Antigen, B-Cell
  • Tamoxifen
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases