Developmental switches in chemokine response profiles during B cell differentiation and maturation

Developing B cells undergo dramatic changes in their responses to chemoattr actant cytokines (chemokines) and in expression of chemokine receptors. Bon e marrow pre-pro-B cells (AA4.1(+)/natural killer 1.1(-) Fraction A cells) and cells capable of generating pro-B colonies in the presence of interleuk in 7 and flt3 ligand migrate to thymus-expressed chemokine (TECK), a respon se lost in later stages of B cell development. B cell-attracting chemokine 1 (BCA-1) responses correlate with CXC chemokine receptor (CXCR)5 expressio n, are first displayed by a pro-B cell subset, are lost in pre-B cells, and then are regained just before and after egress from the marrow. All periph eral B cell subsets, including follicular and germinal center as well as ma rginal zone and peritoneal B1 B cells, respond to BCA-1, implying that resp onsiveness to this follicular chemokine is not sufficient to predict follic le localization. Responses to the CC chemokine receptor (CCR)7 ligands seco ndary lymphoid tissue chemoattractant (SLC) and macrophage inflammatory pro tein (MIP)-3 beta, implicated in homing to lymphoid tissues, are upregulate d before B cell exit from the marrow, but increase further in the periphery and are shared by all peripheral B cells. In contrast, responsiveness to M IP-3 alpha and expression of CCR6 are acquired only after emigration to the periphery and during maturation into the recirculating B cell pool. Chemot axis to stromal cell-derived factor lot is observed at all stages of B cell differentiation. Thus, unique patterns of chemokine responses may help def ine developing B cell populations and direct their maturation in the marrow and migration to the periphery.