Control of the immune response in vitro by calcium ions. I. The antagonistic action of calcium ions on cell proliferation and on cell differentiation.

The effects of Ca on primary and secondary immune responses to SRBC was investigated using the Marbrook technique. During the primary immune response three periods could be distinguished: first, a Ca-independent lag period (0–24 hours after antigenic stimulation); second, a period with an absolute requirement for Ca (24–36 hours after antigenic stimulation), which is related to a proliferative phase of antigenically stimulated cells; and third, a period (later than 48 hours and up to 72 hours after antigenic stimulation), which is inhibited by Ca and which can be enhanced by removing Ca from the medium. This third period is related to the differentiation step(s) leading to antibody-forming cells. During the secondary immune response only a partial inhibition of immune response was observed after removing Ca from the medium at the time of antigenic stimulation. Addition of Ca to EGTA-containing culture medium at any time relative to the initiation of the secondary immune response enhanced the response, but, in contrast to its effects on a primary immune response, never completely restored it. Removal of Ca later than 6 hours after initiation of the response resulted in a decreased inhibition of the immune response and in an increased switch from 19S to 7S antibody-forming cells. This differentiation step was enhanced by removing Ca from the medium and was inhibited by Ca added to the medium. The results suggest that Ca controls the mechanisms involved in the antibody formation by an antagonistic action on cell proliferation and cell differentiation.