Ingénierie cellulaire, Recherche et développement, Héma-Québec, 1070 avenue des Sciences-de-la-Vie, Québec, QC, G1V 5C3, Canada.
Arch Immunol Ther Exp (Warsz). 2011 Feb;59(1):25-40. doi: 10.1007/s00005-010-0108-8. Epub 2011 Jan 14.
Naive and memory B-lymphocyte populations can be activated through the binding of CD154 to CD40, a receptor that is constitutively expressed on the surface of these cells. Models based on the in vitro stimulation of human B lymphocytes through CD40 have greatly contributed to our understanding of the human immune response in healthy individuals and patients suffering from immune disorders. The nature of the engineered CD40 ligands is as diverse as the in vitro models used in studies of CD40-activated B lymphocytes. Monoclonal anti-CD40 antibodies, recombinant CD154 proteins, soluble CD154(+) membranes as well as CD154(+) cell lines have turned out to be very useful tools, and are still in use today. As for any receptor-ligand interaction, parameters such as duration and strength of contact, timing, affinity, and receptor density are major determinants of CD40 binding by CD154 or anti-CD40. Furthermore, variation in the intensity of CD40 stimulation has been shown to influence proliferation, differentiation and immunoglobulin secretion of human hybridomas, B-cell lines, tonsil and blood B lymphocytes. The objective of this review is to present an overview of the great diversity of CD40 agonists used in in vitro models of B-lymphocyte activation, with a particular emphasis on variations in the resulting strength of CD40 signaling generated by these models. A better understanding of these models could open up new avenues for the rational use of human B lymphocytes as antigen-presenting cells in cellular therapies.
幼稚 B 淋巴细胞和记忆 B 淋巴细胞可通过 CD154 与 CD40 的结合而被激活，CD40 是这些细胞表面持续表达的一种受体。通过 CD40 体外刺激人 B 淋巴细胞的模型大大促进了我们对健康个体和免疫紊乱患者的人类免疫反应的理解。工程化 CD40 配体的性质与用于研究 CD40 激活 B 淋巴细胞的体外模型一样多样化。单克隆抗 CD40 抗体、重组 CD154 蛋白、可溶性 CD154(+)膜以及 CD154(+)细胞系已被证明是非常有用的工具，并且至今仍在使用。与任何受体-配体相互作用一样，接触的持续时间和强度、时间、亲和力和受体密度等参数是 CD154 或抗 CD40 与 CD40 结合的主要决定因素。此外，已表明 CD40 刺激强度的变化会影响人杂交瘤、B 细胞系、扁桃体和血液 B 淋巴细胞的增殖、分化和免疫球蛋白分泌。本综述的目的是概述用于 B 淋巴细胞激活体外模型的各种 CD40 激动剂，特别强调这些模型产生的 CD40 信号转导强度的变化。更好地了解这些模型可以为合理利用人类 B 淋巴细胞作为细胞治疗中的抗原呈递细胞开辟新的途径。
