EBI2 was identified by the up-regulation of its expression upon Epstein-Barr virus infection of primary B lymphocytes. EBI2 is predicted to encode a G protein-coupled receptor that is most closely related to the thrombin receptor and signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha. EBI2 is expressed abundantly in lymphoid tissues such as spleen and lymph node, and in B- and T-lymphocytes. It is also highly expressed in lung, heart and gastrointestinal tract, and weakly expressed in the urogenital system and brain. EBI2 is an orphan receptor that plays a central role during humoral immunity and promotes activated B-cell localization in the outer follicle and interfollicular regions. Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses.