The role of human interleukin-6 in B-cell isotype regulation and differentiation.

Human Interleukin-6 (IL-6) is a cytokine secreted by T cells, as well as a variety of other cell types, which exhibits B-cell differentiating activity. The recent cloning of the gene that codes for this molecule has allowed us the opportunity to study the function of this molecule alone and in conjunction with other lymphokines in human B-cell isotype-regulation and differentiation. Recombinant human IL-6 enhances immunoglobulin (Ig) M and G secretion by B-cells activated by Staphylococcal A Cowan strain (SAC) and enhances IgM, IgG, and IgA secretion by B-cells activated by pokeweed mitogen. IL-6 also augments immunoglobulin secretion of differing isotypes from various Epstein-Barr Virus transformed B-cell lines. However, IL-6 does not alter the secreted isotype of naive surface IgM-positive B-cells. As human T-cells secrete other lymphokines in association with IL-6 after activation we examined the interaction of Interleukin-2 (IL-2) gamma-interferon (IFN-gamma) and Interleukin-4 (IL-4) with IL-6 on B-cell immunoglobulin secretion. IL-2 and IL-4 synergized with IL-6 in augmenting immunoglobulin secretion by SAC-activated B-cells. IFN-gamma significantly inhibited the Ig secretion of SAC-activated B-cells cocultured with IL-6 alone or in combination with IL-2. These results demonstrate that human recombinant IL-6 augments immunoglobulin secretion of isotype-committed B-cells but it does not induce a change in the isotype secreted. In addition, this lymphokine synergizes with IL-2 and IL-4 in supporting Ig secretion. However, IFN-gamma significantly inhibits IL-6 induced Ig secretion.