Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells.
The regulation of CCR6 (chemokine receptor 6) expression during B-cell ontogeny and antigen-driven B-cell differentiation was analyzed. None of the CD34(+)Lin(-) hematopoietic stem cell progenitors or the CD34(+)CD19(+) (pro-B) or the CD19(+)CD10(+) (pre-B/immature B cells) B-cell progenitors expressed CCR6. CCR6 is acquired when CD10 is lost and B-cell progeny matures, entering into the surface immunoglobulin D(+) (sIgD(+)) mature B-cell pool. CCR6 is expressed by all bone marrow-, umbilical cord blood-, and peripheral blood-derived naive and/or memory B cells but is absent from germinal center (GC) B cells of secondary lymphoid organs. CCR6 is down-regulated after B-cell antigen receptor triggering and remains absent during differentiation into immunoglobulin-secreting plasma cells, whereas it is reacquired at the stage of post-GC memory B cells. Thus, within the B-cell compartment, CCR6 expression is restricted to functionally mature cells capable of responding to antigen challenge. In transmigration chemotactic assays, macrophage inflammatory protein (MIP)-3alpha/CC chemokine ligand 20 (CCL20) induced vigorous migration of B cells with differential chemotactic preference toward sIgD(-) memory B cells. These data suggest that restricted patterns of CCR6 expression and MIP-3alpha/CCL20 responsiveness are integral parts of the process of B-lineage maturation and antigen-driven B-cell differentiation.
Krzysiek
R
R
Institut National de la Santé et de la Recherche Médicale (INSERM) U 131, Institut Paris-Sud sur les Cytokines, Clamart, France.
Lefevre
E A
EA
Bernard
J
J
Foussat
A
A
Galanaud
P
P
Louache
F
F
Richard
Y
Y
D000199:Actins / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation; D054418:Chemokine CCL20; D019742:Chemokines, CC; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D009101:Multiple Myeloma; D010950:Plasma Cells / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000199:Actins; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D002630:Chemotactic Factors; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D011947:Receptors, Antigen, B-Cell; D054399:Receptors, CCR6; D019707:Receptors, Chemokine