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 (Mφ). HF was adsorbed by both heat killed and live Mφ but the former could not transmit it to B cells. Both the polypeptide chains of HF bind to Mφ. HF remains on the surface of Mφ and can be retrieved completely by contact with B cells for 40 min. The helper signal from TH or HF-adsorbed Mφ 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 Mφ as compared to that by TH alone. Thus, even with lower frequency of TH a significant number ofB cells may be triggered with the help of HF and Mφ. 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 Mφ) and B cells.