B cell activation in peripheral blood and lymph nodes during HIV infection

BACKGROUND: The spontaneous in-vitro antibody synthesis observed in unstimulated lymphocyte cultures from HIV-infected patients closely reflects the in-vivo activation of the B cell compartment; however, the mechanisms underlying this phenomenon are far from clear. METHODS: We compared the ability of peripheral blood mononuclear cells (PBMC) and lymph-node cells (LNC) from 10 HIV-infected patients to produce in vitro HIV-specific and total Ig spontaneously, and we correlated these parameters with tumour necrosis factor alpha (TNF-alpha) expression by CD4 T cells, viral dissemination in the organism, and the extent of HIV spread into lymph-node germinal centres, measured by in-situ hybridization (ISH). RESULTS: In-vitro spontaneous synthesis of both HIV-specific and total antibody was significantly higher in PBMC than in LNC; the two variables showed a good correlation in LNC, but not in PBMC. In both compartments, no correlation was found between B cell activation and the percentage of CD4 T cells expressing TNF-alpha, which was increased compared with seronegative donors. Furthermore, no correlation was found between in-vitro spontaneous antibody synthesis and the number of T cells containing proviral HIV in PBMC and LNC, or the plasma levels of HIV RNA. On the contrary, a good correlation was found between HIV-specific B cell activation and the extent of viral spread into lymph-node germinal centres, evaluated by ISH. CONCLUSION: These data suggest that the adhesion of HIV virions to the follicular dendritic cell network in lymph-node germinal centres may primarily contribute to sustaining the steady B cell activation observed in HIV-infected patients.