title: Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10.
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.
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Matthias
authors.identifier: 0000-0002-0785-5904
authors.initials: M
authors.lastname: Vanderkerken
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pouliot
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Deswarte
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Toussaint
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Karl
authors.initials: K
authors.lastname: Vergote
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Lana
authors.initials: L
authors.lastname: Vandersarren
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Janssens
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|The Laboratory for Protein Biochemistry and Biomolecular Engineering (L-Probe), Ghent University, Ghent, Belgium.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Ramou
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|The Laboratory for Protein Biochemistry and Biomolecular Engineering (L-Probe), Ghent University, Ghent, Belgium.
authors.forename: Savvas N
authors.initials: SN
authors.lastname: Savvides
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
authors.forename: Jody J
authors.initials: JJ
authors.lastname: Haigh
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Rudi
authors.initials: R
authors.lastname: Hendriks
authors.affiliation: Institute for Molecular Health Sciences, ETH, Zürich, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.affiliation: VIB Center for Brain and Disease, VIB, Leuven, Belgium.|Center for Human Genetics, KULeuven, Leuven, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: Craessaerts
authors.affiliation: VIB Center for Brain and Disease, VIB, Leuven, Belgium.|Center for Human Genetics, KULeuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: de Strooper
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Kearney
authors.affiliation: Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
authors.affiliation: VIB Inflammation Research Center, Ghent University, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.|Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
mesh_terms: D000072197:ADAM10 Protein / Q000235:genetics / Q000378:metabolism*; D056704:Adaptive Immunity; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051883:Receptor, Notch2 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C511877:Dll3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497765:Notch2 protein, mouse; D051883:Receptor, Notch2; D011947:Receptors, Antigen, B-Cell; D017346:Protein Serine-Threonine Kinases; C000620906:Tack3 kinase, mouse; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse