Receptor-directed focusing of lymphokine release by helper T cells

The interaction between helper T cells and B cells, leading to the production of antibody to thymus-dependent antigens, was the first cell interaction clearly defined in the immune system1–3; it remains both paradigmatic and controversial. Two requirements of this interaction, that the helper cell (TH) and the B cell must recognize antigenic determinants that are physically linked4,5, and that the TH and the B cell must share genes encoding major histocompati-bility complex (MHC) class II molecules6, led to the concept that TH–B interaction required an intimate physical association of the two cell types. But in vitro studies have shown that TH can be replaced by soluble, antigen-nonspecific factors, capable of activating any B cell to secrete antibody7,8. We have previously proposed that the requirements for TH–B contact might result from TH cells releasing their lymphokines in a polar fashion directed at that portion of the cell membrane where T-cell receptor cross-linking is actually occurring9–16. Using an artificial monolayer of a cloned helper T-cell line, we show that lymphokines are r eleased preferentially over the area of receptor cross-linking under conditions of limited TH-cell activation. Thus, it appears that one important aspect of the specificity of TH–B cell interactions is the receptor-directed polar release of helper lymphokines.