Effects of zidovudine on B lymphocyte activation.

B cell dysfunction associated with HIV infection includes polyclonal B cell activation and hypergammaglobulinemia. There is also an elevated frequency of B cell malignancies, especially non-Hodgkin's lymphoma, in HIV infection. It is believed that chronic polyclonal activation of B cells might increase the chances for the occurrence of a genetic accident, resulting in tumorigenesis. Long-term zidovudine use in people with HIV infection has been reported to be associated with a particularly high incidence of B cell lymphoma. This may be due to an increase in life span associated with antiretroviral treatment, placing treated individuals at risk for developing lymphoma for a greater period of time. However, zidovudine could be directly contributing to lymphoma-genesis in HIV-infected individuals, perhaps by enhancing B cell activation, since B cell hyperactivation and elevated levels of IL-6, a B cell stimulatory cytokine, are seen in HIV infection. Also, people treated with zidovudine may inherently be at higher risk for developing lymphoma because of the relatively greater degree of immune impairment seen in those that receive treatment with this drug. To examine if exposure to zidovudine resulted in enhanced B cell activation, we determined whether or not the presence of zidovudine enhanced B cell activation or IL-6 production in vitro or in vivo. Exposure to zidovudine in vitro did not enhance spontaneous immunoglobulin or IL-6 secretion by cells from HIV-infected (or uninfected) subjects and did not enhance B cell activation induced by EBV or affect the ability of T cells to regulate EBV-activated B cells. Neither serum immunoglobulin or IL-6 levels, nor the expression of cell surface activation markers on circulating B cells, were seen to increase following zidovudine treatment. These results indicate that zidovudine does not induce B cell activation in vivo or in vitro, suggesting that zidovudine treatment does not contribute to lymphomagenesis by enhancing B cell hyperstimulation.