The fate of phytohaemagglutinin-activated human lymphocytes following their peak proliferative activity

Morphological and histochemical studies and cell counts were performed on phytohaemagglutinin-stimulated lymphocyte cultures at intervals from 1 to 17 days. Following a phase of proliferative activity lasting from the second to the sixth days, different cell types became evident in the later stages of culture. Some of the cells were large and characterised by an abundant cytoplasm containing numerous electron-dense bodies with a characteristic internal structure, a well developed Golgi apparatus, a highly irregular plasma membrane, numerous pinocytoses and intense acid phosphatase activity localised within the dense bodies. These cells resembled epithelioid cells in which phagocytic vacuoles were very infrequent. In contrast, phagocytic cells distended with phagocytosed debris were present throughout the period of culture. In later cultures many of the cells were smaller than activated lymphocytes. Intermediate sized cells were characterised by a paucity of organelles and low acid phosphatase activity, and small cells were similar to unstimulated lymphocytes but frequently contained numerous mitochondria. A few cells with a highly developed endoplasmic reticulum were observed at 3 days and also in later stages. The large cells with intense acid phosphatase activity constituted 20-30% of the total cells at 6 days but were more sparse in later stages when intermediate and small lymphocytes predominated. The total cell count on the seventeenth day was 50% of the initial cell count and the cells were almost entirely small, apparently healthy lymphocytes.