Studies on the cellular basis of IgM immunological memory.

(1) A direct experimental method has been used to test whether IgM immunological memory is carried by antibody-forming cells or by cells not releasing detectable antibody. (2) An adoptive transfer system was used to demonstrate memory. Donor mice were injected intravenously (i.v.) with sheep erythrocytes, and at intervals thereafter, dispersed cells from their spleens were transferred to lethally irradiated recipient mice, together with more antigen. The greatly increased plaque-forming cell responses in the spleens of irradiated mice receiving primed as compared to unprimed donor cells was taken as a measure of the level of IgM memory in the donor mice. (3) Suspensions of donor spleen cells were divided mechanically (by micromanipulation) into: (a) a plaque-forming cell fraction, and (b) a fraction totally free of plaque-forming cells. Each fraction was injected, with antigen, into an irradiated recipient mouse, and the response of these mice was compared with that of a third animal which received unfractionated cells. It was consistently found that irradiated mice receiving plaque-free populations of cells responded as well as the controls, while no response was observed in mice receiving donor plaque-forming cells alone. A similar approach showed that the antigen responsiveness of spleen cells from unprimed mice is independent of their content of `background' plaque-forming cells. It is concluded that IgM immunological memory is carried by cells which are not producing plaques, and reasons are discussed for supposing that memory cells and antibody-forming cells belong to separate cell lineages.