Faguet G B, Agee J F
Cancer Immunology Laboratory, Veterans Administration Medical Center, Augusta, GA 30912.
Blood. 1989 Nov 15;74(7):2493-500.
The fate of the common chronic lymphatic leukemia antigen (cCLLa), a leukemia-associated antigen selectively expressed by clonal cells in chronic lymphatic leukemia (CLL) was examined in 31 patients. cCLLa was detected by immune precipitation assay in extracts of metabolically labeled CLL culture cells, in CLL cell culture supernatants, and in patients' sera. In vitro shed membrane cCLLa was comparable in all patients (n = 15) on a per cCLLa-positive cell basis but was independent of cCLLa density (r = .46), absolute lymphocyte count ([ALC] r = .46) and stage (r = .44). In contrast, serum cCLLa (n = 31) correlated with absolute cCLLa-positive cell count (r = .92) and to a lesser extent with stage (r = .67), but was independent of cCLLa density (r = .47). cCLLa modulation was assessed from changes in membrane density estimated by radioreceptor assay before and after in vitro exposure to anti-cCLLa monoclonal antibody (MoAb) CLL2. Immune precipitation studies of metabolically labeled CLL cells showed that modulated cCLLa was internalized as judged by its detection within modulated cells but not in their supernatants. Intact cCLLa-CLL2 complexes were not detected within the modulated cells nor in their supernatants. Regeneration of modulated cCLLa was rapid with return to baseline density levels within 24 hours of antibody removal. Modulation was specific and depended on exposure time, medium temperature, and on antibody titer; correlated with extent of disease (versus absolute lymphocyte count, r = .79; versus stage, r = .66; n = 22); was independent of cCLLa density or affinity (r = .44 to r = .57; n = 11); and was unaffected by T cells or by monocytes (n = 14).
对31例慢性淋巴细胞白血病(CLL)患者中常见慢性淋巴细胞白血病抗原(cCLLa)的命运进行了研究,cCLLa是一种在慢性淋巴细胞白血病中由克隆细胞选择性表达的白血病相关抗原。通过免疫沉淀试验在代谢标记的CLL培养细胞提取物、CLL细胞培养上清液以及患者血清中检测到了cCLLa。在体外,以每个cCLLa阳性细胞为基础,所有患者(n = 15)脱落的膜cCLLa相当,但与cCLLa密度(r = 0.46)、绝对淋巴细胞计数([ALC],r = 0.46)和分期(r = 0.44)无关。相比之下,血清cCLLa(n = 31)与绝对cCLLa阳性细胞计数相关(r = 0.92),与分期的相关性较小(r = 0.67),但与cCLLa密度无关(r = 0.47)。通过放射性受体测定法评估体外暴露于抗cCLLa单克隆抗体(MoAb)CLL2前后膜密度的变化来评估cCLLa的调节。对代谢标记的CLL细胞进行的免疫沉淀研究表明,经调节的cCLLa被内化,这可通过在调节细胞内而非其上清液中检测到它来判断。在调节细胞内及其上清液中均未检测到完整的cCLLa - CLL2复合物。去除抗体后24小时内,经调节的cCLLa迅速再生,恢复到基线密度水平。调节具有特异性,取决于暴露时间、培养基温度和抗体滴度;与疾病程度相关(与绝对淋巴细胞计数相比,r = 0.79;与分期相比,r = 0.66;n = 22);与cCLLa密度或亲和力无关(r = 0.44至r = 0.57;n = 11);且不受T细胞或单核细胞影响(n = 14)。