Pulczynski S, Boesen A M, Jensen O M
University Department of Pathology, Aarhus Amtssygehus, Denmark.
Blood. 1993 Mar 15;81(6):1549-57.
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.
利用荧光显微镜(FM)、流式细胞术(FCM)和免疫电子显微镜(IEM),在NALM - 6、RAJI和JOK - 1细胞系上研究了抗体诱导的CD10和CD19抗原调制(AIAM)。与单克隆抗体(MoAb)交联可诱导CD10和CD19在细胞表面快速重新分布(FM),随后发生内化,包括通过质膜凹陷摄取、通过内体区室转运(受体介导的内吞作用),最后输送到溶酶体进行降解或胞吐和再循环(IEM)。FCM和IEM显示了关于调制和细胞内加工的显著定量差异。因此,在NALM - 6、RAJI和JOK - 1细胞中,分别有35%、30%和25%的CD10被内化,而CD19的内化率分别为80%、60%和40%。此外,与CD10相比,CD19的细胞内转运速率以及外化和再循环速率更明显,并且与JOK - 1细胞相比,NALM - 6和RAJI细胞中的情况也是如此。这些差异可能反映了CD10和CD19的功能意义以及恶性B细胞的分化阶段。尽管这两种抗原在MoAb靶向免疫治疗中都可能有用,但我们的研究结果表明,抗CD19 MoAb在将细胞毒性剂递送至恶性B细胞方面更具优势。