Cognate interactions between helper T cells and B cells. I. Cloning and helper activity of a lymphokine-dependent...

Two essential events in the development of humoral immune responses to thymus-dependent (TD) antigens are the physical interaction of helper T cells (Th) with B cells and the elaboration of Th-derived lymphokines. Understanding the respective contribution of Th-B cell contact vs. lymphokines in triggering B-cell growth and differentiation has been hindered by the capacity of most Th clones to provide both cell contact-dependent and lymphokine-dependent signals. Our approach to study the role of lymphokines in TD B-cell growth and differentiation was to select antigen-specific Th clones that were able to induce class II-restricted B-cell growth and differentiation only in the presence of exogenously added lymphokines. In such a way, selected Th clones would putatively be defective in lymphokine production, but able to provide cell contact-dependent signals. One clone selected in this manner, Th-3.1, has been instrumental in addressing the role of IL4 in TD B-cell responses. Upon co-culture of purified TNP-specific B cells (TNP-ABC), antigen, and Th-3.1, Th-3.1 was unable to induce TNP-ABC growth or differentiation unless an exogenous lymphokine source (EL4 SN) was provided. The reason for the exogenous lymphokine requirement was two-fold. First, it appeared that Th-3.1 required IL2 to produce lymphokines (IL4) essential for B-cell growth and differentiation. Second, even in the presence of antigen and IL2, the level of lymphokine production by Th-3.1 was insufficient to induce optimal B-cell responses. Because an exogenous source of lymphokines was essential for Th-3.1-induced TNP-ABC growth and differentiation, the requirement for specific lymphokines in TD B-cell responses could be addressed. One lymphokine shown to be necessary for Th-3.1-induced TNP-ABC growth and differentiation was IL4. Addition of anti-IL4 to culture or the depletion of IL4 from the exogenous lymphokine source reduced the TD proliferative and antibody response of TNP-ABC. Because the addition of IL4 alone was unable to restore helper activity, it was concluded that IL4 was necessary but not sufficient for TD B-cell growth and differentiation. Pre-incubation of TNP-ABC and IL4 overcame the IL4 requirement when co-cultured with Th-3.1 and antigen.(ABSTRACT TRUNCATED AT 400 WORDS)