Is the activated T helper stimulus able to induce Ig isotype switching in cultured human B cells?

It is confirmed that large amounts of IgM, IgG, and IgA are produced when human B cells are cultured with T cells activated by immobilized CD3 antibody (CD3 system). IL-2 was essential; lower levels of Ig production with different isotype ratios were obtained if IL-4 or IL-6 replaced IL-2. Depletion of sIgG+ or sIgA+ cells from the B population to be cultured markedly reduced production of IgG or IgA. Cultures of B cells selected with the pan-B markers CD19, CD72, or CD21 contained similar levels of Ig of all three isotypes, whereas B cells selected for sIgM or sIgD expression produced IgM but very little IgG or IgA indicating that little isotype switching was occurring. Production of IgG or IgA from cells expressing these isotypes was more efficient than production of IgM from IgM+IgD+ cells. These results are considered in the light of the demonstration by others of the production of multiple isotypes from single sIgM+-selected B cells. Cloned human T cells from a single donor induced production of all three isotypes, but the proportions varied indicating that the potent T-B cell interactions inducing B cell activation may override and conceal the operation of isotype specific cell interactions. Some T clones used at an optimal dose were as effective untreated as X-irradiated, whereas with other clones maximum Ig production was not achieved without irradiation.