Interaction of human thymus-derived and non-thymus-derived lymphocytes in vitro. Induction of proliferation and antibody synthesis in B lymphocytes by a soluble factor released from antigen-stimulated T lymphocytes

Abstract

Relatively pure populations of human T and B lymphocytes were obtained from blood and tonsils using density gradient centrifugation in bovine serum albumin. Antigen alone was incapable of triggering the B lymphocyte into blast transformation or to secrete antibody. However, supernatants from tetanus toxoid-stimulated T cells obtained from immune donors contained a factor mitogenic for B lymphocytes. 50-60% of B cells responded to this lymphocyte mitogenic factor (LMF) by proliferation, loss of C3 reactivity, and change to a secretory state. LMF-stimulated B cells exhibited a three- to fivefold increase in protein secretion and a six- to eightfold increase in gamma G globulin secretion. De novo secreted IgG had specificity directed to the tetanus toxoid present in the LMF containing T-cell supernatants. This was confirmed by an increase in the number of indirect plaque-forming cells to tetanus toxoid-coated sheep red blood cells after stimulation of B cells with LMF. It is proposed that in the course of the response to a previously encountered protein antigen, sensitized human T cells emit a signal in the form of a soluble product that, together with antigen, triggers B cells into division and antibody secretion. The experimental model utilized can be adapted to study human T-B cell cooperation under various conditions in normal individuals and in individuals with immunodeficiency diseases.