Antibody-induced modulation and intracellular transport of CD10 and CD19 antigens in human B-cell lines: an immunofluorescence and immunoelectron microscopy study.
Antibody-induced antigenic modulation (AIAM) of CD10 and CD19 was studied on NALM-6, RAJI, and JOK-1 cell lines using fluorescence microscopy (FM), flow cytometry (FCM), and immunoelectron microscopy (IEM). Cross-linking with monoclonal antibodies (MoAbs) induced rapid redistribution of CD10 and CD19 on the cell surface (FM) followed by internalization involving uptake through plasmalemmal pits, transfer through endosomal compartment (receptor-mediated endocytosis), and, finally, delivery to lysosomes for degradation or exocytosis and recycling (IEM). Significant quantitative differences regarding modulation and intracellular processing were shown by FCM and IEM. Thus, 35%, 30%, and 25% of CD10 compared with 80%, 60%, and 40% of CD19 were internalized in NALM-6, RAJI, and JOK-1 cells, respectively. Also, the rate of intracellular transfer as well as externalization and recycling was more pronounced in the case of CD19 than of CD10 and in the NALM-6 and RAJI cells compared with the JOK-1 cells. These differences may possibly reflect the functional significance of CD10 and CD19 as well as the stage of differentiation of the malignant B cells. Although both antigens can be useful in MoAb-targeted immunotherapy, our findings suggest that anti-CD19 MoAbs would be preferable for delivery of cytotoxic agents to malignant B cells.
Pulczynski
S
S
University Department of Pathology, Aarhus Amtssygehus, Denmark.
Boesen
A M
AM
Jensen
O M
OM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D001692:Biological Transport; D002460:Cell Line; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D015260:Neprilysin / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D015260:Neprilysin