The secreted M1 protein of murine gammaherpesvirus 68 (MHV68) promotes effector Vβ4(+) CD8(+) T cell expansion to impact virus control and immune-mediated pathologies in C57BL/6 mice, but not BALB/c mice. We report a striking increase in the number of genome-positive, IgD(-) B cells during chronic infection of both mouse strains. This suggests a novel role for M1 in influencing long-term maintenance in a major latency reservoir irrespective of the degree of Vβ4(+) CD8(+) T cell expansion.