title: B cell antigen receptor signaling and internalization are mutually exclusive events.
abstract: Engagement of the B cell antigen receptor initiates two concurrent processes, signaling and receptor internalization. While both are required for normal humoral immune responses, the relationship between these two processes is unknown. Herein, we demonstrate that following receptor ligation, a small subpopulation of B cell antigen receptors are inductively phosphorylated and selectively retained at the cell surface where they can serve as scaffolds for the assembly of signaling molecules. In contrast, the larger population of non-phosphorylated receptors is rapidly endocytosed. Each receptor can undergo only one of two mutually exclusive fates because the tyrosine-based motifs that mediate signaling when phosphorylated mediate internalization when not phosphorylated. Mathematical modeling indicates that the observed competition between receptor phosphorylation and internalization enhances signaling responses to low avidity ligands.
authors.affiliation: Department of Medicine and Section of Rheumatology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Hou
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Araujo
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.forename: Don
authors.initials: D
authors.lastname: Massenburg
authors.forename: Margaret
authors.initials: M
authors.lastname: Veselits
authors.forename: Colleen
authors.initials: C
authors.lastname: Doyle
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Dinner
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Clark
mesh_terms: D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000276:immunology; D004705:Endocytosis; D006801:Humans; D007137:Immunoglobulin alpha-Chains / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007137:Immunoglobulin alpha-Chains; D011947:Receptors, Antigen, B-Cell; D014442:Monophenol Monooxygenase; D017479:Receptors, Platelet-Derived Growth Factor