The human gammaherpesviruses Epstein-Barr virus (EBV)and Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 ) are ubiquitous human pathogens that are associated with the development of numerous types of malignancies, including B cell lymphomas. Murine gammaherpesvirus 68 (MHV68) is genetically related to EBV and KSHV and causes lymphoma and lymphoproliferative disease in mice, providing a useful small-animal model for mechanistic in vivo studies of the virus-host relationship. Both the human and murine viruses subvert the antiviral immune response to establish lifelong latent infections in mature B cells. However, it is not clearly understood how these viruses gain access to specific mature B cell subsets or whether latent infection of these subsets is actively maintained over time. One intriguing possibility is that gammaherpesviruses gain entry to the circulating mature B cell compartment via infection of B cell progenitors. Mature B cells arise via a highly regulated, multistep developmental process that results in the daily generation of thousands of new cells. Thus, any developing B cell subsets could provide a potential access point for recurrent entry of the virus into the long-lived mature B cell reservoir.