Mitogenic stimulation of human B lymphocytes via the inositol phospholipid 'dual pathway' of signalling requires persistent activation of both second messenger arms.

Highly purified resting tonsillar B lymphocytes mount an efficient mitogenic response on exposure to appropriate combinations of tumour-promoting phorbol esters and calcium ionophores, agents that mimic the biochemical second messengers generated through the cross-linking of surface immunoglobulins. By using agents that bind reversibly we show here that both signals need to be applied continuously in order for cells to proceed optimally to DNA synthesis. The data are consistent with the notion that, in the absence of 'help' from T lymphocytes or antigen-presenting cells, a chronic, persistent stimulation through antigen receptors is necessary to elicit a significant B-cell response.