Activated B Lymphocytes from Human Immunodeficiency Virus-infected Individuals Induce Virus Expression in Infected T Cells and a Promonocytic Cell Line, U1 By

Freshly isolated B lymphocytes from patients infected with human immunodeficiency virus (HIV), in contrast to B cells from normal controls, were shown to induce viral expression in two cell lines : ACH-2, a T cell line, and Ul, a promonocytic cell line, which are chronically infected with HIV, as well as in autologous T cells . In 10 out of 10 HIVinfected individuals with hypergammaglobulinemia, spontaneous HIV-inductive capacity was found with highly purified peripheral blood B cells, whereas peripheral blood or tonsillar B cells from six healthy, HIV negative donors did not induce HIV expression unless the cells were stimulated in vitro . The induction of HIV expression was observed in direct coculture experiments of B lymphocytes and HIVinfected cells, and could also be mediated by supernatants from cultures of B cells. Significantly higher amounts of interleukin 6 (IL6) and tumor necrosis factor a (TNF-a) were detected in the B cell culture supernatants from HIVinfected patients with hypergammaglobulinemia (IL-6 : z = 536 pg/ml ; TNF-a: x = 493 pg/ml), as compared with normal uninfected controls (IL-6 : x = 18 pg/ml; TNF-a: z = 23 pg/ml) . Antibodies against these cytokines abolished the HIV-inductive capacity of B cells. We conclude that in vivo activated B cells in HIVinfected individuals can upregulate the expression of virus in infected cells by secreting cytokines such as TNF-a and IL6, and, therefore, may play a role in the progression of HIV infection.