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 expres...

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Published inBlood Vol. 96; no. 7; p. 2338
Main Authors Krzysiek, R, Lefevre, E A, Bernard, J, Foussat, A, Galanaud, P, Louache, F, Richard, Y
Format Journal Article
LanguageEnglish
Published United States 01.10.2000
Subjects
Actins - metabolism
B-Lymphocytes - metabolism
B-Lymphocytes - ultrastructure
Cell Differentiation
Chemokine CCL20
Chemokines, CC
Chemotactic Factors - pharmacology
Chemotaxis, Leukocyte
Cytokines - pharmacology
Cytoskeleton - metabolism
Gene Expression Regulation - drug effects
Humans
Lymphoid Tissue - cytology
Macrophage Inflammatory Proteins - pharmacology
Multiple Myeloma
Plasma Cells - cytology
Receptors, Antigen, B-Cell - physiology
Receptors, CCR6
Receptors, Chemokine - genetics
Tumor Cells, Cultured
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Summary: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.
ISSN:0006-4971