title: Polarized secretion of lysosomes at the B cell synapse couples antigen extraction to processing and presentation.
abstract: Engagement of the B cell receptor (BCR) by surface-tethered antigens (Ag) leads to formation of a synapse that promotes Ag uptake for presentation onto major histocompatibility complex class II (MHCII) molecules. We have highlighted the membrane trafficking events and associated molecular mechanisms involved in Ag extraction and processing at the B cell synapse. MHCII-containing lysosomes are recruited to the synapse where they locally undergo exocytosis, allowing synapse acidification and the extracellular release of hydrolases that promote the extraction of the immobilized Ag. Lysosome recruitment and secretion results from the polarization of the microtubule-organizing center (MTOC), which relies on the cell division cycle (Cdc42)-downstream effector, atypical protein kinase C (aPKCζ). aPKCζ is phosphorylated upon BCR engagement, associates to lysosomal vesicles, and is required for their polarized secretion at the B cell synapse. Regulation of B lymphocyte polarity therefore emerges as a central mechanism that couples Ag extraction to Ag processing and presentation.
authors.affiliation: Inserm U932, Institut Curie, 12 rue Lhomond, 75005 Paris, France. maria-isabel.yuseff@curie.fr
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Yuseff
authors.forename: Anne
authors.initials: A
authors.lastname: Reversat
authors.forename: Danielle
authors.initials: D
authors.lastname: Lankar
authors.forename: Jheimmy
authors.initials: J
authors.lastname: Diaz
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fanget
authors.forename: Paolo
authors.initials: P
authors.lastname: Pierobon
authors.forename: Violaine
authors.initials: V
authors.lastname: Randrian
authors.forename: Nathanael
authors.initials: N
authors.lastname: Larochette
authors.forename: Fulvia
authors.initials: F
authors.lastname: Vascotto
authors.forename: Chantal
authors.initials: C
authors.lastname: Desdouets
authors.forename: Bertrand
authors.initials: B
authors.lastname: Jauffred
authors.forename: Yohanns
authors.initials: Y
authors.lastname: Bellaiche
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gasman
authors.forename: François
authors.initials: F
authors.lastname: Darchen
authors.forename: Claire
authors.initials: C
authors.lastname: Desnos
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Lennon-Duménil
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D016764:Cell Polarity; D054992:Immunological Synapses; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D011493:Protein Kinase C / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000276:immunology
chemical_list: D011947:Receptors, Antigen, B-Cell; C115015:PKC-3 protein; D011493:Protein Kinase C; D020764:cdc42 GTP-Binding Protein