Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3 alpha/CCL20 in human B cells

The regulation of CCR6 (chemokine receptor 6) expression during B-cell onto geny and antigen-driven B-cell differentiation was analyzed. None of the CD 34(+)Lin(-) hematopoietic stem cell progenitors or the CD34(+)CD19(+) (pro- B) or the CD19(+)CD10(+) (pre-B/immature B cells) B-cell progenitors expres sed CCR6. CCR6 is acquired when CD10 is lost and B-cell progeny matures, en tering into the surface immunoglobulin D+ (slgD(+)) mature B-cell pool. CCR 6 is expressed by all bone marrow-, umbilical cord blood-, and peripheral b lood-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 respondin g to antigen challenge. In transmigration chemotactic assays, macrophage in flammatory protein (MIP)-3 alpha/CC chemokine ligand 20 (CCL20) induced vig orous migration of B cells with differential chemotactic preference toward slgD(-) memory B cells. These data suggest that restricted patterns of CCR6 expression and MIP-3 alpha/CCL20 responsiveness are integral parts of the process of B-lineage maturation and antigen-driven B-cell differentiation. (Blood.2000;96:2338-2345) (C) 2000 by The American Society of Hematology.