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

Abstract

The effects of Ca⁺⁺ on primary and secondary immune responses to SRBC in vitro 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.