IL-4-induced expression of germline γ1 transcripts in B cells following cognate interactions with T helper cells

Abstract

T cell-dependent B cell activation and the induction of isotype switching require antigen and direct contact with helper T (Th) cells. During activation, B cells can switch from the expression of IgM to that of IgG, IgE or IgA, depending on the lymphokines secreted by the Th cell with which they interact. Studies of lipopolysaccharide (LPS)-activated B cells have suggested that lymphokines regulate isotype switching via a transcriptional mechanism that increases the accessibility of downstream C_H genes to a switch recombinase(s). To assess the roles of T cell contact and lymphokines in isotype switching, we have examined the accessibility model for the regulation of isotype switching to lgG1 in the context of cognate interactions between Th cells and normal B cells. We demonstrate that Th2 cells that secrete IL-4 can induce expression of germline γ1 transcripts in B cells. The steady-state level of germline γ1 transcripts induced by Th2 cells is enhanced as compared with the level induced by IL-4 alone or IL-4 and LPS also alters the relative usage of the germline γ1 transcription initiation sites. Enhanced expression of germline γ1 transcripts requires direct contact between T and B cells suggesting a rote for T cell contact-mediated signals in regulating the accessibility of switch regions.