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静脉注射用免疫球蛋白体外抑制商陆丝裂原诱导的B细胞分化的细胞机制

Cellular mechanisms in the in vitro inhibition of pokeweed mitogen-induced B cell differentiation by immunoglobulin for intravenous use.

作者信息

Stohl W

出版信息

J Immunol. 1986 Jun 15;136(12):4407-13.

PMID:2940294
Abstract

Polyspecific monomeric IgG for i.v. use (IgSRK; Sandoglobulin) can inhibit in vitro pokeweed mitogen (PWM)-induced B cell differentiation. This antigen-nonspecific inhibition is an early event, because removal of the IgSRK from cultures of PWM-stimulated peripheral blood mononuclear cells (PBMC) after as short a period as 24 hr could not reverse the inhibitory effects. Furthermore, replacement of the IgSRK-exposed T cells after 48 hr of culture with fresh autologous T cells could not abrogate the inhibition. In addition, IgSRK exerted an inhibitory effect on non-T cells even before their activation by PWM. Neither augmentation of T suppressor activity nor inhibition of T helper activity could be demonstrated as a consequence of interaction with IgSRK. Irradiation of the T cells before culture, supplementing the culture medium with exogenous interleukin 2, monocyte depletion, or depletion of the Leu-11+ population had no effect on the IgSRK-mediated inhibition. Tonsil cells were as susceptible to the inhibitory effects of IgSRK as were unseparated PBMC. Taken together, these experiments point to a direct inhibitory effect of IgSRK on the B cell in this antigen-nonspecific system. However, minor roles for monocytes, T cells, and/or Leu-11+ cells cannot be excluded. This inhibitory capacity of IgSRK might be efficacious clinically in the treatment of autoimmune disorders in which pathogenic autoantibodies play a role. However, such treatment might also inhibit desired antibody responses to vaccinations and/or infectious agents.

摘要

静脉注射用多特异性单体IgG(IgSRK;桑多球蛋白)可在体外抑制商陆有丝分裂原(PWM)诱导的B细胞分化。这种抗原非特异性抑制是一个早期事件,因为在短至24小时后从PWM刺激的外周血单个核细胞(PBMC)培养物中去除IgSRK并不能逆转抑制作用。此外,在培养48小时后用新鲜的自体T细胞替换暴露于IgSRK的T细胞并不能消除抑制作用。此外,IgSRK甚至在非T细胞被PWM激活之前就对其发挥抑制作用。与IgSRK相互作用的结果既未显示出T抑制活性增强,也未显示出T辅助活性受到抑制。培养前对T细胞进行照射、用外源性白细胞介素2补充培养基、单核细胞耗竭或Leu-11+群体耗竭对IgSRK介导的抑制作用均无影响。扁桃体细胞与未分离的PBMC一样易受IgSRK的抑制作用影响。综上所述,这些实验表明在这个抗原非特异性系统中IgSRK对B细胞具有直接抑制作用。然而,不能排除单核细胞、T细胞和/或Leu-11+细胞发挥的次要作用。IgSRK的这种抑制能力在临床上可能对治疗致病性自身抗体起作用的自身免疫性疾病有效。然而,这种治疗也可能抑制对疫苗接种和/或感染因子的理想抗体反应。

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