Transmission of dengue virus-induced helper signal to B cell via macrophages

Abstract

The helper T cells (TH) generated in dengue type 2 virus (DV) infection of mice produce a soluble helper cytokine (HF) which enhances the clonal expansion of DV-specific IgM antibody plaque forming cells (PFC). The present study was undertaken to investigate the mechanism of transmission of the helper signal from TH and HF to B cells. It was observed that TH could transmit the helper signal to B cells by direct cell to cell contact, but HF could not do so without the presence of live macrophages (M phi). HF was adsorbed by both heat killed and live M phi but the former could not transmit it to B cells. Both the polypeptide chains of HF bind to M phi. HF remains on the surface of M phi and can be retrieved completely by contact with B cells for 40 min. The helper signal from TH or HF-adsorbed M phi could not be transmitted to B cells when they were separated from each other by a cell impermeable membrane. The enhancement of PFC count is greater when the signal is transmitted by HF-adsorbed M phi as compared to that by TH alone. Thus, even with lower frequency of TH a significant number of B cells may be triggered with the help of HF and M phi. The findings thus show that the DV-specific helper signal could be transmitted only by a close physical contact of the plasma membranes of the signal presenting cells (TH or HF-adsorbed M phi) and B cells.