Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells.
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.
Muehlinghaus
Gwendolin
G
Deutsches Rheumaforschungszentrum, Department for Humoral Immunology, Schumannstrasse 21/22, D-10117 Berlin, Germany.
Cigliano
Luisa
L
Huehn
Stephan
S
Peddinghaus
Anette
A
Leyendeckers
Heike
H
Hauser
Anja E
AE
Hiepe
Falk
F
Radbruch
Andreas
A
Arce
Sergio
S
Manz
Rudolf A
RA
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
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