Granule formation in large granular lymphocytes (LGL). Ultrastructural and cytochemical studies on cells from patients with abnormally expanded lgl populations.
The peripheral blood mononuclear cells from five patients with abnormally expanded populations of large granular lymphocytes (LGL) of possible malignant origin have been studied by electron microscopy. These cells had fewer granules than normal circulating LGL but displayed a variety of organelles possibly involved in the process of granule formation. This process apparently originated from the fusion of vesicles that had a characteristic cup-shape (and appeared to be derived from the Golgi apparatus) with smaller vesicles, mostly of the coated type. This fusion resulted in the formation of multivesicular bodies (MVB) whose limiting membrane was constituted by that of the cup-shaped vesicle. MVB gradually matured into electron-dense granules. A number of cup-shaped vesicles were found positive for the cytochemical localization of thiamine pyrophosphatase (TPP) activity that is a specific marker of the trans aspect of the Golgi apparatus, a finding which confirmed that they were Golgi-derived. The smaller, mostly coated, vesicles were positive for acid phosphatase (AP) and evidence was obtained indicating that they subserved the function of transporting acid hydrolases from the rough endoplasmic reticulum to the cup-shaped vesicles or to the MVB. The plasma membrane did not appear to contribute to MVB or granule formation since endocytic vacuoles induced by reacting the cell surface with the appropriate monoclonal antibodies (followed by peroxidase labelled anti-immunoglobulin) were never seen while fusing with granules or MVB. Rather, these vesicles formed secondary lysosomes after having encountered smooth or, more rarely, coated vesicles. Granulogenesis in LGL, therefore, resembles the process of granule formation observed in secretory cells. The active process of granulogenesis detected in the patient cells and a number of other findings indicate that they were LGL at early stages of maturation. The surface phenotype consistently found in these cells (OKT3+, Leu 1+, OKT8+, Leu 2a+, OKT11+, Leu 5+ and OKM1) is different from that of the majority of the normal LGL and may correspond to that of immature LGL.
D000135:Acid Phosphatase / Q000032:analysis; D000328:Adult; D000368:Aged; D003594:Cytoplasmic Granules / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000201:enzymology / Q000473:pathology*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D013834:Thiamine Pyrophosphatase / Q000032:analysis
D000135:Acid Phosphatase; D013834:Thiamine Pyrophosphatase