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

Academic Article

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.
  • Published In

  • Nature Immunology  Journal
  • Keywords

  • ADAM10 Protein, Adaptive Immunity, Amyloid Precursor Protein Secretases, Animals, B-Lymphocytes, Cell Differentiation, Cell Lineage, Cells, Cultured, Clonal Selection, Antigen-Mediated, Gene Expression Regulation, Germinal Center, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein-Serine-Threonine Kinases, Receptor, Notch2, Receptors, Antigen, B-Cell, Signal Transduction
  • Digital Object Identifier (doi)

    Author List

  • Hammad H; Vanderkerken M; Pouliot P; Deswarte K; Toussaint W; Vergote K; Vandersarren L; Janssens S; Ramou I; Savvides SN
  • Start Page

  • 313
  • End Page

  • 320
  • Volume

  • 18
  • Issue

  • 3