title: IL-17 superfamily cytokines modulate normal germinal center B cell migration.
abstract: The germinal center (GC) is a dynamic structure formed by proliferating B cells in the follicles of secondary lymphoid organs during T cell-dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs), and a light zone where CBs migrate and transform into centrocytes (CCs), a minority of which is selected to survive, undergoes Ig class-switch recombination, and differentiates into memory B cells or long-lived plasma cells. CBs express CXCR4 and are attracted to the dark zone by stromal cell-derived CXCL12, whereas CCs express CXCR5 and are recruited to the light zone along a gradient of CXCL13 produced by follicular dendritic cells (FDCs). Therefore, CXCL12 and CXCL13 play crucial roles in the regulation of GC B cell trafficking. Among the numerous molecules involved in GC formation, IL-17A represents a recent addition. Its involvement has been demonstrated in mouse models of human autoimmune or infectious diseases. IL-17A belongs to the IL-17 cytokine superfamily, together with 5 additional structurally related cytokines. We have recently demonstrated that IL-17A renders freshly isolated tonsil GC B cells competent to migrate to CXCL12 and CXCL13 through a NF-κBp65-dependent mechanism. Here, we review the role of IL-17A on GC cells and discuss, for the first time, common effects of the cognate cytokines IL-25 and IL-17B on GC B cell function.
authors: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italia; and.
authors: Elisa
authors: E
authors: Ferretti
authors: Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milano, Italy.
authors: Maurilio
authors: M
authors: Ponzoni
authors: Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milano, Italy.
authors: Claudio
authors: C
authors: Doglioni
authors: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italia; and vitopistoia@gaslini.org.
authors: Vito
authors: V
authors: Pistoia
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002465:Cell Movement; D060833:Cellular Microenvironment; D018925:Chemokines / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D005810:Multigene Family; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology
chemical_list: D018925:Chemokines; C508717:IL17A protein, human; C486701:IL25 protein, human; D020381:Interleukin-17; D019707:Receptors, Chemokine
keywords: GC; IL-17B; IL-25