Changing responsiveness to chemokines allows medullary plasmablasts to leave lymph nodes

During T cell-dependent antibody responses lymph node B cells differentiate either to plasmablasts that grow in the medullary cords, or to blasts that proliferate in follicles forming germinal centers. Many plasmablasts diffe rentiate to plasma cells locally, but some leave the medullary cords and mi grate to downstream lymph nodes. To assess the basis for this migration, ch anges in the responsiveness of B cells to a range of chemokines have been s tudied as they differentiate. Naive B cells express high levels of CCR6, CC R7, CXCR4 and CXCR5. When activated B cells grow in follicles the expressio n of these chemokine receptors and the responsiveness to the respective che mokines is retained. During the extrafollicular response, plasmablast expre ssion of CXCR5 and responsiveness to B-lymphocyte chemoattractant (CXCR5) a s well as to secondary lymphoid tissue chemokine (CCR7) and stromal cell-de rived factor(SDF)-1 (CXCR4) are lost while a weak response towards the CCR6 chemokine LARC is maintained. Despite losing responsiveness to SDF-1, extr afollicular plasmablasts still express high levels of CXCR4 on the cell sur face. These results suggest that the combined loss of chemokine receptor ex pression and of chemokine responsiveness may be a necessary prerequisite fo r cells to migrate to the medullary cords and subsequently enter the effere nt lymph.