Differential response of malignant human B-cells to anti-IgM immunoglobulin (anti-mu) and B-cell growth factor: unique direct cytotoxicity of anti-mu on prolymphocytic leukemia cells

作者: CS Chan , F Soehnlen , GP Schechter

DOI: 10.1182/BLOOD.V76.8.1601.1601

关键词:

摘要: We examined in vitro tritiated thymidine uptake by B cells from seven prolymphocytic leukemia (PLL), chronic lymphocytic (CLL), and four plasma cell (PCL) patients response to culture with anti-human IgM antibody (anti-mu) B-cell growth factor (BCGF). In contrast the stimulatory effect observed normal cultures, divalent F(ab')2 anti-mu uniquely inhibited autonomous proliferation induced marked cytotoxicity six of PLL cultures independent complement or Fc-receptor-mediated mechanisms. There was neither stimulation inhibition slgM+ CLL slgM- PCL cells. The inhibitory on at an concentration below threshold for Significant impairment trypan blue exclusion delayed until 48 hours, morphological cellular changes suggestive a programmed death mechanism apoptosis. slgM-staining intensity BCGF-augmented DNA synthetic activity similar de novo transformation CLL. Cells patient were separated elutriation into two fractions, BCGF-unresponsive large "transformed" fraction synthesis smaller lymphoid subset low 3H-thymidine that could be augmented BCGF. Both fractions equally susceptible cytotoxic anti-mu. These data suggest certain slgM-bearing malignant are anti-mu-triggered cytotoxicity. They may represent counterpart "tolerogenic" subset, unique direct provide therapeutic strategy specifically PLL.

参考文章(18)
R I Mishell, A L DeFranco, J P Jakway, M R Gold, W R Usinger, Growth regulation of the B lymphoma cell line WEHI-231 by anti-immunoglobulin, lipopolysaccharide, and other bacterial products. Journal of Immunology. ,vol. 137, pp. 2225- 2231 ,(1986)
T Tadakuma, C Odaka, H Kizaki, T cell receptor-mediated DNA fragmentation and cell death in T cell hybridomas. Journal of Immunology. ,vol. 144, pp. 2096- 2101 ,(1990)
Tadao Miyake, Yoshio Nishizawa, Yuichi Yamamura, Tadamitsu Kishimoto, Takeshi Watanabe, Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. Journal of Immunology. ,vol. 115, pp. 1179- 1184 ,(1975)
H Kubagawa, M D Cooper, S Maruyama, Activation of human B cells and inhibition of their terminal differentiation by monoclonal anti-mu antibodies. Journal of Immunology. ,vol. 135, pp. 192- 199 ,(1985)
A L DeFranco, E S Raveche, W E Paul, Separate control of B lymphocyte early activation and proliferation in response to anti-IgM antibodies. Journal of Immunology. ,vol. 135, pp. 87- 94 ,(1985)
B. Trauth, C Klas, A. Peters, S Matzku, P Moller, W Falk, K. Debatin, P. Krammer, Monoclonal antibody-mediated tumor regression by induction of apoptosis Science. ,vol. 245, pp. 301- 305 ,(1989) , 10.1126/SCIENCE.2787530
Christopher A. Smith, Gwyn T. Williams, Rosetta Kingston, Eric J. Jenkinson, John J. T. Owen, Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature. ,vol. 337, pp. 181- 184 ,(1989) , 10.1038/337181A0
Michio Kawano, Koji Iwato, Hideki Asaoku, Osamu Tanabe, Hideo Tanaka, Hideaki Ishikawa, Nobutaka Imamura, Atsushi Kuramoto, Heterogenous response of B cell chronic lymphocytic leukaemia (B-CLL) cells to anti-human IgM antibody (anti-μ) and B cell stimulatory factor 1 (BSF-1) British Journal of Haematology. ,vol. 71, pp. 47- 51 ,(1989) , 10.1111/J.1365-2141.1989.TB06273.X
Thomas R. Baeker, Thomas L. Rothstein, Effects of anti-IgM on mitogen-induced proliferation of human B-lymphocyte malignancies Clinical Immunology and Immunopathology. ,vol. 39, pp. 285- 297 ,(1986) , 10.1016/0090-1229(86)90092-9