Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10.
Hamida HammadMatthias VanderkerkenPhilippe PouliotKim DeswarteWendy ToussaintKarl VergoteLana VandersarrenSophie JanssensIoanna RamouSavvas N SavvidesJody J HaighRudi HendriksManfred KopfKatleen CraessaertsBart de StrooperJohn F KearneyDaniel H ConradBart N LambrechtPublished in: Nature immunology (2017)
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.
Keyphrases
- poor prognosis
- induced apoptosis
- cell cycle arrest
- acute lymphoblastic leukemia
- tyrosine kinase
- binding protein
- cell proliferation
- endoplasmic reticulum stress
- cell fate
- stem cells
- signaling pathway
- adipose tissue
- type diabetes
- protein kinase
- cell therapy
- single cell
- endothelial cells
- bone marrow
- high glucose
- mesenchymal stem cells
- high fat diet induced