PRIMING OF HELPER T-CELL-DEPENDENT ANTIBODY-RESPONSES BY HEMAGGLUTININ-TRANSGENIC B-CELLS

Mice expressing the hemagglutinin (HA) gene of influenza virus PR8 (H1 sub-type) under the control of chi light chain promoter and enhancer have been generated. They express HA in and on B cells, and are tolera nt to HA. In vitro, only lipopolysaccharide (LPS) blasts but not resti ng B cells of transgenic mice can stimulate HA-specific helper T cells of HA-specific alpha/beta T cell receptor (TCR)-transgenic mice. Tran sfer of PIX-transgenic LPS blasts into syngeneic, non-transgenic recip ients primes HA-specific antibody responses. Resting, small HA-transge nic B cells, which were purified by fluorescence-activated cell sortin g, prime lower antibody responses. Host B cells produce the HA-specifi c antibody response. The donor HA-transgenic B cells need to express m ajor histocompatibility complex (MHC) class II molecules and need to h e alive to induce the antibody response in the host. Most notably, the host antibody response never produces detectable levels of IgM, but o nly of switched IgG isotypes. Neither resting nor activated HA-transge nic B cells induce tolerance in antibody responses. These results sugg est that HA-transgenic B cells, presenting both the intact antigen on the cell surface and peptides of the antigen on MHC class II, are effe ctive inducers of helper T cell responses, and as judged by the Ig-iso type response pattern, which is mainly IgG1, of Th2 type.