In summary, our study for the first time defines CD11c<sup>+</sup> splenic B cells as a reservoir of latent gammaherpesvirus during mucosal chronic infection and reveals an important role of T-bet<sup>+</sup> B cells in controlling long-term infection and gammaherpesvirus-driven pathogenic host processes.IMPORTANCEGammaherpesviruses are ubiquitous pathogens that are associated with cancer and multiple sclerosis. Here, ITGAX is linked to cancer.