The duration of specific antibody titers ranges from a few weeks up to several years. While the formation of antibody secreting plasma cells takes place in secondary lymphoid tissues, long-lasting antibody responses are provided by bone marrow plasma cells. The majority of plasma cells initially formed remains in secondary lymphoid tissues and die within a few days. Plasma cells that migrate into the bone marrow or into chronically inflamed tissues can survive for much longer periods of time. The capacity of plasma blasts to migrate into these tissues is regulated by chemokine receptors. Expression of CXCR4 is important for plasma cell migration into the bone marrow. CXCR3 ligands expressed in large quantities in chronically inflamed tissues (e.g. in effected kidneys in systemic lupus erythematosus) and can attract plasmablasts, thus mediating plasma cell accumulation at those sites. Here we analyzed the regulation of chemokine receptor expression during plasma cell differentiation in culture. Purified CXCR3-negative B cells were activated T dependently in a two-step culture system, for 3 days by CD40 ligand together with IL-2 and IL-10 and for 5 more days with IL-2 and IL-10. Alternatively, cells were stimulated T independently with CpG, IL-2 and IL-10. Addition of IFN-γ or monocyte/T-cell culture supernatant in the initial culture, but not at late stages, induced the expression of CXCR3 on plasma cells, thus suggesting that the regulation of this receptor is an early event during plasma cell differentiation. In contrast, CXCR4 was present on all plasma cells, formed under any stimulation conditions and even when CXCR4-negative B cells were activated to form plasma cells. These data indicate that expression of CXCR4 and, as a consequence, the potential to migrate into the bone marrow is generally associated with differentiation into plasma cells, whereas the expression of CXCR3 must be induced by the inflammatory cytokine IFN-γ.