Quantitation of the number of mitogen molecules activating DNA synthesis in T and B lymphocytes.

Thymus-derived (T) and bone-marrow-derived (B) lymphocytes bound equal numbers of Concanavalin A (Con A) molecules, although only T cells were stimulated to proliferation by soluble Con A. Optimal T cell proliferation occurred when approximately 3 × 10 molecules of Con A were bound per cell, which corresponds to 3–10% of the available receptors. Con A can be converted to a selective B cell mitogen provided it was presented to the cells in a locally concentrated form, achieved by cross-linking the lectin to the bottom of tissue culture Petri dishes. Optimal B cell stimulation by insolubilized Con A was obtained at a density of 1–4 × 10 molecules/cm. It was estimated that per unit surface area, B and T cells were activated by the same number of Con A molecules, whereas T cells required more molecules per cell. In terms of T–B cell co-operation this suggests that optimally activated T cells present an optimally stimulating number of Con A molecules to the B cells by direct cell to cell interaction. It is postulated that the actual interaction between Con A and the sugar containing receptor at the cell membrane is not directly responsible for lymphocyte activation, but as a consequence of this initial binding, the Con A-receptor complex interacts with a second membrane receptor of a different type. When a sufficient number of these second receptors have reacted with the Con A-sugar receptor complex the cell became activated. T cells are postulated to have a greater number of the second type receptors than B cells. The ability of locally concentrated Con A to activate B cells but not T cells is explained in terms of this hypothesis.