Immunoglobulin and cytokine expression in mixed lymphocyte cultures is reduced by disruption of gap junction intercellular communication

Connexins (Cx), the protein subunits assembled into gap junction intercellu lar communication channels, are expressed in primary lymphoid or organs and by circulating leukocytes, Human tonsil-derived T and B lymphocytes expres s Cx40 and 43; circulating human T, B, and NK lymphocytes express Cx43 and directly transfer between each other a low molecular dye indicative that fu nctional gap junctions exist. We now identify specific properties in the im mune system underwritten by gap junctions. Mixed lymphocytes cultured in th e presence of two reagents with independent inhibitory action on gap juncti on communication, a connexin mimetic peptide and 18-alpha -glycyrrhetinic a cid, markedly reduced the secretion of IgM, Igc, and IgA. The secretion of these immunoglobulins by purified B cells was also reduced by the two class es of gap junction inhibitors. Complex temporal inhibitory effects on the e xpression of mRNA encoding interleukins, especially IL-10, were also observ ed, The results indicate that intercellular signaling across gap junctions is an important component of the mechanisms underlying metabolic cooperatio n in the immune system.