Priming of helper T cell‐dependent antibody responses by hemagglutinin‐transgenic B cells

Abstract

Mice expressing the hemagglutinin (HA) gene of influenza virus PR8 (H1 subtype) under the control of x light chain promoter and enhancer have been generated. They express HA in and on B cells, and are tolerant to HA. In vitro, only lipopolysaccharide (LPS) blasts but not resting B cells of transgenic mice can stimulate HA‐specific helper T cells of HA‐specific α/β T cell receptor (TCR)‐transgenic mice. Transfer of HA‐transgenic LPS blasts into syngeneic, non‐transgenic recipients primes HA‐specific antibody responses. Resting, small HA‐transgenic B cells, which were purified by fluorescence‐activated cell sorting, prime lower antibody responses. Host B cells produce the HA‐specific antibody response. The donor HA‐transgenic B cells need to express major histocompatibility complex (MHC) class II molecules and need to be alive to induce the antibody response in the host. Most notably, the host antibody response never produces detectable levels of IgM, but only of switched IgG isotypes. Neither resting nor activated HA‐transgenic B cells induce tolerance in antibody responses. These results suggest that HA‐transgenic B cells, presenting both the intact antigen on the cell surface and peptides of the antigen on MHC class II, are effective inducers of helper T cell responses, and as judged by the Ig‐isotype response pattern, which is mainly IgG1, of Th2 type.