Zupo S, Dono M, Azzoni L, Chiorazzi N, Ferrarini M
Istituto Nazionale per la Ricerca sul Cancro, I.S.T., Servizio di Immunologia Clinica, Genova, Italy.
Eur J Immunol. 1991 Feb;21(2):351-9. doi: 10.1002/eji.1830210216.
Tonsillar resting B cells were separated into CD5+ and CD5- cell subsets and stimulated with the thymus-independent mitogens, Staphylococcus aureus Cowan strain I (SAC) or insolubilized anti-mu monoclonal antibodies (a mu Ab). CD5+ cells incorporated [3H]thymidine more efficiently than unfractionated cells when stimulated with SAC and their response was augmented by the addition of interleukin (IL) 2 to the cultures. CD5+ cells also proliferated in response to a mu Ab provided that IL 2 was present, SAC-, but not a mu Ab-stimulated CD5+ cells produced IgM and IgG molecules when IL 2 was added to the cultures and also secreted autoantibodies with rheumatoid factor activity and sometimes also with anti-single-stranded, but not double-stranded, DNA activity. The efficient response of CD5+ cells was not explained by the fact that they contained cells already activated in vivo. Thus, they did not express the CD23, CD69, CD71 and CD39 activation markers, failed to incorporated [3H]thymidine and to secrete Ig spontaneously or in response to IL 2 and were found to be in a quiescent state by cell cycle flow cytometric analysis. In contrast to CD5+ cells, CD5- cells displayed very little or no [3H]thymidine incorporation in response to SAC or to a mu Ab and their poor responsiveness was not altered by changing either the doses of the stimulants, the timing of the cultures, by co-culturing the cells together with CD5+ cells, or by adding IL 2 or IL 4. Immunofluorescence studies showed that freshly prepared CD5- cells did not have surface activation markers but that they expressed them following SAC stimulation. Thus, unlike that observed for CD5+ cells, SAC seems to be capable of activating CD5- cells but does not appear to be a sufficient stimulus for driving the cells into the subsequent phases of the cell cycle. The above findings, that demonstrate marked differences in the response to CD5+ and CD5- cells to thymus-independent stimuli, may bear relevance for the understanding of the normal clonal expansion of CD5+ cells as well as for the pathogenesis of autoimmune diseases.
扁桃体静止B细胞被分离为CD5 +和CD5 -细胞亚群，并用胸腺非依赖性丝裂原、金黄色葡萄球菌考恩I株（SAC）或不溶性抗μ单克隆抗体（抗μ抗体）进行刺激。当用SAC刺激时，CD5 +细胞比未分离的细胞更有效地掺入[3H]胸腺嘧啶核苷，并且通过向培养物中添加白细胞介素（IL）2可增强其反应。只要存在IL 2，CD5 +细胞也会对抗μ抗体作出反应而增殖，添加IL 2到培养物中时，SAC刺激而非抗μ抗体刺激的CD5 +细胞产生IgM和IgG分子，并且还分泌具有类风湿因子活性的自身抗体，有时还分泌具有抗单链而非双链DNA活性的自身抗体。CD5 +细胞的有效反应不能用它们含有体内已被激活的细胞这一事实来解释。因此，它们不表达CD23、CD69、CD71和CD39激活标志物，不能自发地或在对IL 2作出反应时掺入[3H]胸腺嘧啶核苷并分泌Ig，并且通过细胞周期流式细胞术分析发现它们处于静止状态。与CD5 +细胞相反，CD5 -细胞对SAC或抗μ抗体的反应几乎没有或完全没有掺入[3H]胸腺嘧啶核苷，并且通过改变刺激剂的剂量、培养时间、将细胞与CD5 +细胞共同培养或添加IL 2或IL 4，其低反应性并未改变。免疫荧光研究表明，新鲜制备的CD5 -细胞没有表面激活标志物，但在SAC刺激后会表达它们。因此，与CD5 +细胞不同，SAC似乎能够激活CD5 -细胞，但似乎不是驱动细胞进入细胞周期后续阶段的充分刺激。上述发现表明CD5 +和CD5 -细胞对胸腺非依赖性刺激的反应存在显著差异，这可能与理解CD5 +细胞的正常克隆扩增以及自身免疫性疾病的发病机制有关。
