Polyclonal mitogenesis of human lymphocytes by PWM: Two preprogrammed division cycles resulting in cells refractile to further mitogenesis

Pokeweed mitogen (PWM) is known to induce human peripheral blood lymphocytes to enter S phase as well as B lymphocytes to differentiate into plasmacytes. The proliferation induced by PWM was characterized by population size, mitotic index, and flow cytometric measurements. Analysis of these data using a mathematical model of induced proliferation shows that lymphocytes exposed to PWM undergo two division cycles. The first incorporates a long lag and is approximately 87 hr long. The second division cycle is shorter and is approximately 39 hr. Following the second division cycle, cell cycle transit is arrested in G 1. The arrest is not due to nutritional deficiency or exhaustion of mitogen. Restimulation or feeding of proliferating cells fails to prolong this proliferation. Although the cells undergo two division cycles, the maximum increase in population size was only approximately twofold because of cell loss due to cell death. The analysis indicates that PWM-stimulated cells apparently execute a preordained program of two unequal division cycles followed by terminal quiescence in G 1 0 .