title: Essential role of immobilized chemokine CXCL12 in the regulation of the humoral immune response.
abstract: Chemokines control the migration of a large array of cells by binding to specific receptors on cell surfaces. The biological function of chemokines also depends on interactions between nonreceptor binding domains and proteoglycans, which mediate chemokine immobilization on cellular or extracellular surfaces and formation of fixed gradients. Chemokine gradients regulate synchronous cell motility and integrin-dependent cell adhesion. Of the various chemokines, CXCL12 has a unique structure because its receptor-binding domain is distinct and does not overlap with the immobilization domains. Although CXCL12 is known to be essential for the germinal center (GC) response, the role of its immobilization in biological functions has never been addressed. In this work, we investigated the unexplored paradigm of CXCL12 immobilization during the germinal center reaction, a fundamental process where cellular traffic is crucial for the quality of humoral immune responses. We show that the structure of murine germinal centers and the localization of GC B cells are impaired when CXCL12 is unable to bind to cellular or extracellular surfaces. In such mice, B cells carry fewer somatic mutations in Ig genes and are impaired in affinity maturation. Therefore, immobilization of CXCL12 is necessary for proper trafficking of B cells during GC reaction and for optimal humoral immune responses.
authors.affiliation: Department of Immunology, Unité Lymphopoïèse, Institut Pasteur, 75015 Paris, France.|INSERM U1223, 75015 Paris, France.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Barinov
authors.affiliation: Department of Virology, Unité de Pathogénie Virale, Institut Pasteur, 75015 Paris, France.|INSERM U819, 75015 Paris, France.
authors.forename: Lingjie
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Virology, Unité de Pathogénie Virale, Institut Pasteur, 75015 Paris, France.|INSERM U819, 75015 Paris, France.
authors.forename: Pamela
authors.initials: P
authors.lastname: Gasse
authors.affiliation: Department of Cell Biology & Infection, Unité d'Analyse d'Images Biologiques, Institut Pasteur, 75015 Paris, France.|CNRS UMR 3691, 75015 Paris, France.
authors.forename: Vannary
authors.initials: V
authors.lastname: Meas-Yedid
authors.affiliation: Institut Cochin, INSERM U1016, 75014 Paris, France.|CNRS UMR 8104, 75014 Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Donnadieu
authors.affiliation: Department of Virology, Unité de Pathogénie Virale, Institut Pasteur, 75015 Paris, France; paulo.vieira@pasteur.fr fernando.arenzana-seisdedos@pasteur.fr.|INSERM U819, 75015 Paris, France.|Institut Pasteur de Shanghai, Chinese Academy of Sciences, 200032 Shanghai, China.
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.affiliation: Department of Immunology, Unité Lymphopoïèse, Institut Pasteur, 75015 Paris, France; paulo.vieira@pasteur.fr fernando.arenzana-seisdedos@pasteur.fr.|INSERM U1223, 75015 Paris, France.
authors.forename: Paulo
authors.initials: P
authors.lastname: Vieira
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology*; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology; D015870:Gene Expression; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D055767:Immobilized Proteins / Q000235:genetics / Q000276:immunology*; D056724:Immunity, Humoral; D007114:Immunization; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012756:Sheep; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D015703:Antigens, CD; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D055767:Immobilized Proteins; D007136:Immunoglobulins
keywords: CXCL12; germinal center reaction; humoral immune responses