Splawski J B, McAnally L M, Lipsky P E
Department of Pediatrics, Harold C Simmons Arthritis Research Center, Dallas, Texas.
J Immunol. 1990 Jan 15;144(2):562-9.
The effect of rIL-6 on the growth and differentiation of highly purified human peripheral blood B cells was examined. IL-6 alone induced minimal incorporation of [3H]thymidine by unstimulated or Staphylococcus aureus (SA)-stimulated B cells and did not augment proliferation induced by SA and IL-2. Similarly, IL-6 alone did not support the generation of Ig-secreting cells (ISC) or induce the secretion of Ig by unstimulated or SA-stimulated B cells. However, IL-6 did augment the generation of ISC and the secretion of all isotypes of Ig induced by SA and IL-2. Maximal enhancement of B cell responsiveness by IL-6 required its presence from the initiation of culture. Delaying the addition of IL-6 to B cells stimulated with SA and IL-2 beyond 24 h diminished its effect on ISC generation. However, increased Ig production but not ISC generation was observed when IL-6 was added to B cells that had been preactivated for 48 h with SA and IL-2. This effect was most marked when the activated B cells were also stimulated with IL-2. IL-6 in combination with other cytokines such as IL-1 and IL-4 did not induce the secretion of Ig or generation of ISC in the absence of IL-2. Moreover, antibody to IL-6 did not inhibit the effect of IL-2 on the growth and differentiation of B cells stimulated with SA, but did inhibit the IL-6-induced augmentation of Ig secretion by B cells stimulated with SA and IL-2. IL-6 alone enhanced T cell dependent induction of B cell differentiation stimulated by PWM. Part of this enhancement was related to its capacity to increase the production of IL-2 in these cultures. These results indicate that IL-6 has several direct enhancing effects on the differentiation of B cells, all of which are at least in part dependent on the presence of IL-2. In addition, IL-6 can indirectly increase B cell differentiation by increasing IL-2 production by T cells.
研究了重组人白细胞介素-6（rIL-6）对高度纯化的人外周血B细胞生长和分化的影响。单独的IL-6仅诱导未刺激或经金黄色葡萄球菌（SA）刺激的B细胞对[3H]胸苷的微量掺入，且不增强SA和IL-2诱导的增殖。同样，单独的IL-6不支持分泌免疫球蛋白的细胞（ISC）的产生，也不诱导未刺激或经SA刺激的B细胞分泌免疫球蛋白。然而，IL-6确实增强了SA和IL-2诱导的ISC的产生以及所有免疫球蛋白同种型的分泌。IL-6对B细胞反应性的最大增强作用需要在培养开始时就存在。将IL-6添加到经SA和IL-2刺激的B细胞中的时间推迟超过24小时会减弱其对ISC产生的影响。然而，当将IL-6添加到已用SA和IL-2预激活48小时的B细胞中时，观察到免疫球蛋白产生增加，但ISC产生未增加。当活化的B细胞也用IL-2刺激时，这种效果最为明显。在没有IL-2的情况下，IL-6与其他细胞因子如IL-1和IL-4联合使用不会诱导免疫球蛋白的分泌或ISC的产生。此外，抗IL-6抗体不抑制IL-2对经SA刺激的B细胞生长和分化的作用，但确实抑制IL-6诱导的经SA和IL-2刺激的B细胞免疫球蛋白分泌的增强。单独的IL-6增强了由美洲商陆有丝分裂原（PWM）刺激的T细胞依赖性B细胞分化诱导。这种增强的部分原因与其增加这些培养物中IL-2产生的能力有关。这些结果表明，IL-6对B细胞分化有几种直接增强作用，所有这些作用至少部分依赖于IL-2的存在。此外，IL-6可通过增加T细胞产生IL-2来间接增加B细胞分化。
