Expression and function of IL-12 and IL-18 receptors on human tonsillar B cells

IL-12 activates murine and human B cells, but little information is availab le as to the expression and function of IL-12R on human B lymphocytes. Here we show that the latter cells, freshly isolated from human tonsils, expres sed the transcripts of both beta1 and beta2 chains of IL-12R and that beta2 chain mRNA was selectively increased (4- to 5-fold) by incubation with Sta phylococcus aureus Cowan I bacteria or IL-12, B cell stimulation with IL-12 induced de novo expression of the transcripts of the two chains of IL-18R, i,e,, IL-1 receptor-related protein and accessory protein-like. Functional studies showed that both IL-12 and IL-18 signaled to B cells through the N F-kappaB pathway. In the case of IL-12, no involvement of STAT transcriptio n factors, and in particular of STAT-4, was detected. c-rel and p50 were id entified as the members of NF-kappaB family involved in IL-12-mediated sign al transduction to B cells. IL-12 and IL-18 synergized in the induction of IFN-gamma production by tonsillar B cells, but not in the stimulation of B cell differentiation, although either cytokine promoted IgM secretion in cu lture supernatants, Finally, naive but not germinal center or memory, tonsi llar B cells were identified as the exclusive IL-12 targets in terms of ind uction of NF-kappaB activation and of IFN-gamma production.