title: Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells.
abstract: C-X-C motif chemokine receptor 3 (CXCR3) and CXCR4 expressed on immunoglobulin G (IgG)-plasma-cell precursors formed in memory immune responses are crucial modulators of the homing of these cells. Here, we studied the regulation of the expression of these chemokine receptors during the differentiation of human memory B cells into plasma cells. We show that CXCR3 is absent on CD27- naive B cells but is expressed on a fraction of memory B cells, preferentially on those coexpressing IgG1. On differentiation into plasma-cell precursors, CXCR3+ memory B cells maintain the expression of this chemokine receptor. CXCR3- memory B cells up-regulate CXCR3 and migrate toward concentration gradients of its ligands only when costimulated with interferon gamma (IFN-gamma), but not interleukin 4 (IL-4), IL-1beta, IL-6, IFN-alpha, IFN-beta, or tumor necrosis factor alpha (TNF-alpha). In contrast, the differentiation of CXCR4- B cells into plasma cells is generally accompanied by the induction of CXCR4 expression. These results show that lack of CXCR4 expression on plasma-cell precursors is not a limiting factor for plasma-cell homing and that the expression of CXCR3 on memory B cells and plasma-cell precursors is induced by IFN-gamma, provided in human T helper type 1 (Th1)-biased immune responses. Once induced in memory B cells, CXCR3 expression remains part of the individual cellular memory.
authors.affiliation: Deutsches Rheumaforschungszentrum, Department for Humoral Immunology, Schumannstrasse 21/22, D-10117 Berlin, Germany.
authors.forename: Gwendolin
authors.initials: G
authors.lastname: Muehlinghaus
authors.forename: Luisa
authors.initials: L
authors.lastname: Cigliano
authors.forename: Stephan
authors.initials: S
authors.lastname: Huehn
authors.forename: Anette
authors.initials: A
authors.lastname: Peddinghaus
authors.forename: Heike
authors.initials: H
authors.lastname: Leyendeckers
authors.forename: Anja E
authors.initials: AE
authors.lastname: Hauser
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Sergio
authors.initials: S
authors.lastname: Arce
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Manz
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D007371:Interferon-gamma