Potential mechanisms of persistent monoclonal gammopathy in patients with chronic HIV infection. Memory B cells are reservoirs of EBV infection. Poor control of HIV viral replication may result in polyclonal B-cell activation, possibly as a result of T-cell deficiency caused by HIV infection. This in turn may lead to persistent EBV replication and terminal differentiation of EBV-infected memory B cells to plasma cells. This is reflected as persistent monoclonal gammopathy, detectable in the peripheral blood. Alternative explanations may be that the EBV-infected memory B cells may act as stimulators of plasma cells or that the observed increased numbers of EBV-infected memory B cells and increased numbers of plasma cells may be independent of one another. Future functional studies are needed to better characterize mechanisms leading to persistent monoclonal gammopathy in HIV-infected patients. Professional illustration by Debra T. Dartez.