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 1gA are produced w hen human B cells are cultured with T cells activated by immobilized C D3 antibody (CD3 system). IL-2 was essential; lower levels of Ig produ ction with different isotype ratios were obtained if IL-4 or IL-6 repl aced IL-2. Depletion of slgG+ or slgA+ cells from the B population to be cultured markedly reduced production of IgG or IgA. Cultures of B c ells selected with the pan-B markers CD19, CD72, or CD21 contained sim ilar levels of Ig of all three isotypes, whereas B cells selected for slgM or slgD expression produced IgM but very little IgG or IgA indica ting that little isotype switching was occurring. Production of IgG or IgA from cells expressing these isotypes was more efficient than prod uction of IgM from IgM+IgD+ cells. These results are considered in the light of the demonstration by others of the production of multiple is otypes from single slgM+-selected B cells. Cloned human T cells from a single donor induced production of all three isotypes, but the propor tions varied indicating that the potent T - B cell interactions induci ng B cell activation may override and conceal the operation of isotype specific cell interactions. Some T clones used at an optimal dose wer e as effective untreated as X-irradiated, whereas with other clones ma ximum Ig production was not achieved without irradiation.