Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands.
Oncode Institute, Utrecht, Netherlands.
Front Immunol. 2021 Nov 17;12:717324. doi: 10.3389/fimmu.2021.717324. eCollection 2021.
B cells and T cells are key players in the defence against infections and malignancies. To exert their function, B cells and T cells differentiate into effector and memory cells. Tight regulation of these differentiation processes is key to prevent their malfunction, which can result in life-threatening disease. Lymphocyte differentiation relies on the appropriate timing and dosage of regulatory molecules, and post-transcriptional gene regulation (PTR) is a key player herein. PTR includes the regulation through RNA-binding proteins (RBPs), which control the fate of RNA and its translation into proteins. To date, a comprehensive overview of the RBP expression throughout lymphocyte differentiation is lacking. Using transcriptome and proteome analyses, we here catalogued the RBP expression for human B cells and T cells. We observed that even though the overall RBP expression is conserved, the relative RBP expression is distinct between B cells and T cells. Differentiation into effector and memory cells alters the RBP expression, resulting into preferential expression of different classes of RBPs. For instance, whereas naive T cells express high levels of translation-regulating RBPs, effector T cells preferentially express RBPs that modulate mRNA stability. Lastly, we found that cytotoxic CD8 and CD4 T cells express a common RBP repertoire. Combined, our study reveals a cell type-specific and differentiation-dependent RBP expression landscape in human lymphocytes, which will help unravel the role of RBPs in lymphocyte function.
B 细胞和 T 细胞是抗感染和恶性肿瘤的主要防御力量。为了发挥其功能，B 细胞和 T 细胞分化为效应细胞和记忆细胞。这些分化过程的严格调控是防止其功能障碍的关键，因为功能障碍可能导致危及生命的疾病。淋巴细胞分化依赖于调节分子的适当时间和剂量，而转录后基因调控 (PTR) 是其中的关键环节。PTR 包括通过 RNA 结合蛋白 (RBP) 进行的调控，RBP 控制 RNA 的命运及其翻译为蛋白质。迄今为止，缺乏整个淋巴细胞分化过程中 RBP 表达的综合概述。使用转录组和蛋白质组分析，我们在此对人类 B 细胞和 T 细胞的 RBP 表达进行了编目。我们观察到，尽管总体 RBP 表达是保守的，但 B 细胞和 T 细胞之间的相对 RBP 表达是不同的。分化为效应细胞和记忆细胞会改变 RBP 的表达，导致不同类别的 RBP 优先表达。例如，幼稚 T 细胞表达高水平的翻译调节 RBP，而效应 T 细胞优先表达调节 mRNA 稳定性的 RBP。最后，我们发现细胞毒性 CD8 和 CD4 T 细胞表达共同的 RBP 库。总之，我们的研究揭示了人类淋巴细胞中具有细胞类型特异性和分化依赖性的 RBP 表达图谱，这将有助于揭示 RBP 在淋巴细胞功能中的作用。
