Tpa-induced maturation in secretory human B-leukemic cells in vitro: DNA
synthesis, antigenic changes, and immunoglobulin secretion
AP Efremidis, H Haubenstock, JF Holland and JG Bekesi
The maturation of malignant cells in response to differentiating agents is
interesting as a model of normal differentiation. The response of a freshly
explanted neoplastic population of phenotypically well- characterized
lymphosarcoma cell leukemia blasts was studied after incubation with the
differentiating agent TPA (12-0-tetradecanoyl- phorbol-13-acetate).
Terminal differentiation was assessed by measuring the immunoglobulin
secreted in culture supernatants and the production of intracytoplasmic
immunoglobulins. Activation of the cells was studied using
fluorescein-labeled monoclonal antibodies to various antigens in a flow
cytometer (fluorescence-activated cell sorter) and 3H-thymidine (3H-Tdr)
incorporation was evaluated to measure DNA synthesis in cells grown in
complete medium and TPA-supplemented medium. The events induced by TPA were
characteristic of B cell maturation and included morphological changes to
plasmacytoid cells, reduction in surface immunoglobulins (sIgM, sIgD, and
K), enhancement of cytoplasmic immunoglobulin, and amplification of
immunoglobulin secretion. Surface antigen changes were accompanied by
increased 3H-Tdr incorporation. Cell proliferation and differentiation
appeared to be coupled and both were amplified by TPA treatment. These
observations indicate that TPA can promote maturation of malignant
secretory B cells to a terminal differentiation stage. The significance of
these findings to normal B cell differentiation and their potential
clinical utility is discussed.
Volume 66,
Issue 4,
pp. 953-960,
10/01/1985
Copyright © 1985 by The American Society of Hematology
