Abstract : Toll-like receptor 9 agonists such as unmethylated bacterial CpG DNAs activate B lymphocytes direct    more

Abstract : Toll-like receptor 9 agonists such as unmethylated bacterial CpG DNAs activate B lymphocytes directly, potentially influencing their function and homeostasis. To assess B cell responsiveness to TLR9 agonists in HIV disease, we examined the ability of naïve and memory B cells to proliferation and to increase surface expression of CD80 in response to CpG oligonucleotides (ODNs). CpG ODN induced expression of CD80 similarly in B cells from HIV-infected persons and from healthy controls. In contrast, proliferation responses to CpG ODN were markedly impaired in both naïve and memory B cell subsets from HIV-infected persons. Naïve B cell proliferation defects were related to plasma HIV RNA and among memory B cells, to the frequencies of CD21-negative cells. Importantly, TLR9 mRNA levels were significantly diminished in freshly prepared naïve B cells and especially so in memory B cells from HIV+ viremic donors suggesting a possible underlying mechanism for the observed functional impairments. Dose response studies indicated that optimal induction of CD80 expression was achieved with much lower concentrations of CpG ODN than optimal induction of proliferation. We propose that the relatively low threshold of activation that is required for CD80 induction by CpG ODN might explain the preservation of this response in B cells from HIV-infected persons despite diminished TLR9 expression. Impaired responsiveness to TLR9 agonists may contribute to defects in humoral immunity in HIV infection. - Slides    less