A coordinated change in chemokine responsiveness guides plasma cell movements

Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic r ed pulp, lymph node medullary cords, and bone marrow. The factors that regu late plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chem otactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they down regulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is express ed within splenic red pulp and lymph node medullary cords as well as in bon e marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver c ells, plasma cells are mislocalized in the spleen, found in elevated number s in blood, and fail to accumulate normally in the bone marrow. Our finding s indicate that as B cells differentiate into plasma cells they undergo a c oordinated change in chemokine responsiveness that regulates their movement s in secondary lymphoid organs and promotes lodgment within the bone marrow .