AbstractHuman alloreactive helper T cell clones were isolated from a secondary mixed lymphocyte reaction by limiting dilution in the presence of irradiated stimulator cells and T cell growth factor (interleukin 2). When cultured with B cells and macrophages possessing the relevant alloantigens, the T cell clones proliferated and induced a strong B cell activation with production of high immunoglobulin levels. Limiting dilution of the B cells from the peripheral blood showed that about one in 5–10 can be activated to produce IgG, one in 10 IgM, one in 20–40 IgA and one in 2000–5000 IgE. Following stimulation by the relevant alloantigen, the clones were able to help also B cells that lacked the alloantigen, indicating that a direct T‐B cell interaction is not required.This method is particularly interesting because it is suitable for the clonal analysis of a B cell subset that is triggered in the absence of antigen by an unrestricted T ce