Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10
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.
|Persistent URL||dx.doi.org/10.1038/ni.3657, hdl.handle.net/1765/108056|
|Grant||This work was funded by the European Commission 7th Framework Programme; grant id erc/261231 - Role of Endoplasmic Reticulum Stress in dendritic cells and immune-mediated lung diseases (ERSTRESS)|
Hammad, H, Vanderkerken, M. (Matthias), Pouliot, P, Deswarte, K, Toussaint, W, Vergote, K, … Lambrecht, B.N.M. (2017). Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10. Nature Immunology, 18(3), 313–320. doi:10.1038/ni.3657