The mechanism involved in the maintenance of staphylococcal enterotoxin B (SEB)-induced T cell anergy is poorly understood. We demonstrated earlier that B cells play an important role in the maintenance of SEB-induced T cell anergy in vivo and in vitro. Here, we demonstrate that B cells are not essential in SEB-induced T cell activation, but are important for the maintenance of T cell memory phenotype and anergy in vivo. Studying the activated B cell repertoire, we observe that SEB treatment increases serum anti-Vβ8 antibody titer as detected by enzyme-linked immunosorbent assay using soluble Vβ8 chains as antigens, and by staining of a Vβ8-expressing thymoma. These antibodies disappear gradually after immunization with SEB, whereas the capacity of the T cells to respond to SEB in vitro is restored. Anti-Vβ8 monoclonal antibody treatment causes Vβ8+ T cell unresponsiveness to SEB in vitro (anergy), without affecting CD4Vβ8+ T cell frequency. Together, these results suggest a new mechanism to explain the maintenance of SEB-induced T cell anergy, which is depen dent on B cells and on anti-Vβ8 antibody that specifically interacts with Vβ8+ T cells.</p