Cellular interaction and the environment in lymphocyte development: the roles of antigen, histocompatibility, and growth factors in T cell-dependent B cell stimulation.

T cell-dependent B cell stimulation depends on cellular interactions between macrophages, T cells, and B cells. T cells recognize antigen in the context of Ia determinants on macrophages. This leads to the activation of helper T cells and to the production of helper factor(s) either by the activated helper T cells or by the macrophages. Cloned lines of helper T cells produce factors("help') for B cell replication and Ig secretion in the presence of histocompatible macrophages and of specific antigen. These factors stimulate histocompatible, as well as histoincompatible, mitogen-activated B cell blasts polyclonally. Thus, neither antigen nor histocompatibility, but antigen-unspecific, soluble factors are required to stimulate an activated B cell blast through the next round of division. Small resting B cells, however, are not stimulated to replication by these factors, but only to polyclonal, H-2-unrestricted maturation to Ig-secreting cells. Replication (and Ig secretion) of small resting B cells, however, is only induced when antigen-specific small B cells bind their specific antigen via surface Ig molecules and interact with histocompatible helper T cells. The preference of the resting B cells for such collaboration with T cell help is mapped to the K-end of the H-2 locus and probably constitutes the antigen expressed on B cells by the I region. It appears that a resting B cell is excited by the binding of specific antigen to surface Ig and by the interaction of its surface Ia with helper T cells. After this dual recognition the excited B cell can be stimulated by the antigen-unspecific factor(s) generated by the interaction of helper T cells, adherent cells and antigen to initiate growth. Immune induction of a B cell thus involves three controlling elements: Ig, Ia, and B cell growth factor receptors.