In the early phase of thymus-dependent antibody responses antigen-engaged B cells rapidly change their localization within the secondary lymphoid organs to access helper T cells. Central to this process is the tightly controlled distribution of chemokines, sphingosine-1-phosphate and other guidance cues within the lymphoid organ, determined in part by the stromal cells, and the changing responsiveness of activated lymphocytes to these cues. Studies that use the emerging technique of real-time two-photon imaging of intact lymphoid organs began to dissect the dynamics of B cell migration before and after antigen engagement in vivo. Recent studies also provided new insight into antigen transport mechanisms in lymphoid organs and examined signaling requirements for B lymphocyte positioning and motility. Taken together, these studies have provided a more detailed map of the steps involved in B cell migration to encounter antigen and helper T cells early during the adaptive immune response.