Perri R T, Kay N E
Department of Medicine, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Am J Hematol. 1989 Jul;31(3):166-72. doi: 10.1002/ajh.2830310305.
Large granular lymphocytes (LGL) may exert regulatory influences on B cell immunoglobulin synthesis. We, therefore, investigated the influence of LGL from controls and B cell chronic lymphocytic leukemia patients (B-CLL) on control B cell proliferation to costimulation with the F(ab')2 fragment of goat antihuman mu and B cell growth factor (BCGF). Purified LGL (greater than 90% by morphology) from control and B-CLL peripheral blood were added in various concentrations to purified control B cells and incubated with anti-mu and BCGF for 3 days. [3H]-thymidine uptake of B cells was then measured. There was no proliferation of control or CLL LGL alone to the costimulatory signals of the F(ab')2 fragments of goat antihuman mu chain and BCGF. Addition of control LGL to equal numbers of control B cells did not blunt control B cell responsiveness to BCGF (with control LGL 8,649 +/- 298 cpm vs. control B cells alone 8,336 +/- 556 cpm, mean +/- SEM). When control LGL were increased to 10:1 LGL:B cell ratio, the maximal inhibition by control LGL of control B cell proliferative response to BCGF was 23%. In contrast, addition of CLL LGL at a 1:1 LGL:B cell ratio resulted in marked impairment of the control B cell proliferative response to BCGF (with CLL LGL 3,586 +/- 954 cpm vs. control B cells alone 8,649 +/- 298 cpm). Inhibition by CLL LGL occurred in a cell-concentration-dependent manner. No difference in CLL LGL's inhibitory effect on either resting or activated control B cell responsiveness to BCGF was noted. Inhibition of de novo protein synthesis (by cycloheximide inhibition) of CLL LGL did impair CLL LGL's inhibitory capacity for BCGF-induced B cell proliferation. A possible explanation for these findings includes the possibility that a subgroup of LGL with B cell suppressive activity may have expanded as a host response to the B cell leukemia or as part of the disordered cell regulation in B-CLL.
大颗粒淋巴细胞（LGL）可能对B细胞免疫球蛋白合成发挥调节作用。因此，我们研究了来自健康对照者和B细胞慢性淋巴细胞白血病患者（B-CLL）的LGL对对照B细胞增殖的影响，这些B细胞通过山羊抗人μ链F(ab')2片段和B细胞生长因子（BCGF）进行共刺激。将来自对照和B-CLL外周血的纯化LGL（形态学鉴定纯度大于90%）以不同浓度加入纯化的对照B细胞中，并与抗μ链抗体和BCGF一起孵育3天。然后测量B细胞的[3H] - 胸腺嘧啶核苷摄取量。单独的对照或CLL LGL对山羊抗人μ链F(ab')2片段和BCGF的共刺激信号均无增殖反应。将对照LGL加入等量的对照B细胞中，并未减弱对照B细胞对BCGF的反应性（对照LGL组为8,649±298 cpm，单独对照B细胞组为8,336±556 cpm，平均值±标准误）。当对照LGL与B细胞的比例增加到10:1时，对照LGL对对照B细胞对BCGF增殖反应的最大抑制率为23%。相比之下，以1:1的LGL:B细胞比例加入CLL LGL会导致对照B细胞对BCGF的增殖反应明显受损（CLL LGL组为3,586±954 cpm，单独对照B细胞组为8,649±298 cpm）。CLL LGL的抑制作用呈细胞浓度依赖性。未观察到CLL LGL对静息或活化的对照B细胞对BCGF反应性的抑制作用有差异。用环己酰亚胺抑制CLL LGL的从头蛋白质合成确实损害了CLL LGL对BCGF诱导的B细胞增殖的抑制能力。这些发现的一个可能解释包括，具有B细胞抑制活性的LGL亚群可能作为宿主对B细胞白血病的反应而扩大，或者作为B-CLL中紊乱的细胞调节的一部分。
