T helper cell membranes promote IL-4-independent expression of germ-line Cγ1 transcripts in B cells

Studies using plasma membranes from activated Th cell clones (Th membranes) to stimulate B cells have shown that both a contact-mediated activation signal plus Th-derived cytokines are required for antibody production. In order to clearly separate and define the role of these two signals in isotype switching, B cells were stimulated with Th membranes in the presence or absence of cytokines, and the transcriptional activity of the unrearranged H chain loci was determined. In the presence of Th membranes, two known switch factors were shown to specifically induce germ-line transcription of the same H chain loci as in LPS-stimulated B cells (IL-4 induced Cγ1 and Cε transcription, transforming growth factor-β induced Cα transcription). The contact-mediated activation signal provided by the Th membranes, in the absence of any added cytokines, resulted in the specific induction of Cγ1 germ-line transcription, and thus functioned as a switch signal for IgG1. These findings provide a mechanism for previously observed IL-4-independent isotype switching to IgG1.