Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10

Nat Immunol. 2017 Mar;18(3):313-320. doi: 10.1038/ni.3657. Epub 2017 Jan 9.

Abstract

Notch2 and B cell antigen receptor (BCR) signaling determine whether transitional B cells become marginal zone B (MZB) or follicular B (FoB) cells in the spleen, but it is unknown how these pathways are related. We generated Taok3-/- mice, lacking the serine/threonine kinase Taok3, and found cell-intrinsic defects in the development of MZB but not FoB cells. Type 1 transitional (T1) B cells required Taok3 to rapidly respond to ligation by the Notch ligand Delta-like 1. BCR ligation by endogenous or exogenous ligands induced the surface expression of the metalloproteinase ADAM10 on T1 B cells in a Taok3-dependent manner. T1 B cells expressing surface ADAM10 were committed to becoming MZB cells in vivo, whereas T1 B cells lacking expression of ADAM10 were not. Thus, during positive selection in the spleen, BCR signaling causes immature T1 B cells to become receptive to Notch ligands via Taok3-mediated surface expression of ADAM10.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM10 Protein / genetics
  • ADAM10 Protein / metabolism*
  • Adaptive Immunity*
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism*
  • Animals
  • B-Lymphocytes / physiology*
  • Cell Differentiation*
  • Cell Lineage*
  • Cells, Cultured
  • Clonal Selection, Antigen-Mediated
  • Gene Expression Regulation
  • Germinal Center / immunology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptor, Notch2 / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction

Substances

  • Dll3 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Notch2 protein, mouse
  • Receptor, Notch2
  • Receptors, Antigen, B-Cell
  • Protein-Serine-Threonine Kinases
  • Tack3 kinase, mouse
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • Adam10 protein, mouse