During antibody responses, B cells undergo a series of migratory events that guide them to the appropriate microenvironments for activation and differentiation. Epstein–Barr virus-induced molecule 2 [EBI2; also known as G-protein-coupled receptor (GPR)183] is a key chemotactic receptor guiding B cell localization. EBI2 and its ligand, 7α,25-dihydroxycholesterol, direct the migration of activated B cells to interfollicular and outer follicular regions of secondary lymphoid tissues. Moreover, modulation of EBI2 expression is crucial for the generation of extrafollicular plasma cell responses and germinal center formation. Here, we review the current findings that have delineated the function of EBI2 and its ligand and discuss how they collaborate with conventional lymphoid chemokine systems to position B cells optimally during immune responses.