The activation of resting lymphocytes is accompanied by the biogenesis of lysosomal organelles.
The degradative activity of lymphocytes plays by important role in a number of essential immune functions. In the present study we have examined how the activation of resting lymphocytes, by the mitogen concanavalin A (Con A), affects three major components of the lysosomal compartment: the lysosomal enzyme beta-glucuronidase (Gus); an integral lysosomal membrane protein (LAMP-1); and the mannose 6-phosphate receptor (MPR) which directs lymphocyte enzyme transport. Resting T cells were found to contain only very low levels of these proteins, but they were actively synthesized by, and far more abundant in, stimulated lymphoblasts. Although the lysosomal antigens did not have a distinct cytoplasmic localization in the resting lymphocytes, in the activated T lymphoblasts they were present in several highly developed intracellular structures, including the rough endoplasmic reticulum and the Golgi complex. Furthermore, in these latter cells Gus was also found to be accumulated within the lumen of large vesicles which we characterized as lysosomes by the presence of LAMP-1 at the periphery and by the absence of MPR. Subcellular fractionation confirmed that these organelles were present in the activated lymphocytes only, and not in the resting T cells. Our results demonstrate that lymphocyte activation is accompanied by the synthesis of the enzymic and structural components of the lysosomal compartment which are sorted and assembled into distinct organelles in the activated cell.
Olsen
I
I
Cell Enzymology Unit, Kennedy Institute of Rheumatology, London.
Bou-Gharios
G
G
Abraham
D
D
D000818:Animals; D015703:Antigens, CD; D003208:Concanavalin A / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000201:enzymology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism; D013347:Subcellular Fractions; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure
D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D003208:Concanavalin A; D005966:Glucuronidase