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.
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