Virgin T cells do not provide help for antigen-specific B cells in the absence of IL-4, IL-5, and IL-6.

We have used a mAb, 23G2, directed against the B exon of the murine CD45 molecule to identify and separate two subpopulations of normal peripheral CD4+ T cells. Examination of these two subpopulations indicates that they correspond to virgin (TV) (CD45RBhi) and memory (Tm) (CD45RBlo) cells. In this report we have determined the abilities of TV and Tm cells to provide antigen-specific, cognate help to hapten-specific antigen-binding B cells. To this end we have enriched Tv and Tm cell populations from splenic CD4+ T cells and have cultured these cells with TNP-specific antigen-binding cells (TNP-ABCs) and specific antigen. We then examined the ability of Tv and Tm cells to promote Ig secretion by the B cells. Both Tm and Tv cells interact with antigen-presenting B cells as assessed by proliferation and lymphokine secretion. However, Tm, but not Tv, cells promote substantial Ig secretion by TNP-ABCs in the presence of antigen. When either IL-6 or IL-4 plus IL-5 are added to cultures of Tc cells, B cells and antigen, Ig secretion is restored. Thus, Tv cells interact effectively with B cells to induce an activation signal, but in the absence of IL-4 plus IL-5 or IL-6 lymphokines, which are not secreted by Tv cells, these cells do not provide help for an antibody response. Hence, naive, peripheral Tv cells must undergo an antigen-dependent differentiation step into Tm and secrete IL-4, IL-5, and IL-6 before they can induce B cells to secrete antibody.