The proteome of B cell maturation identifies PDCD4 as limiting the response of marginal zone B cells – marginal zone B cells WT and PDCD4 KO

During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. We used high-resolution mass spectrometry to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription- and translation initiation-factors that define cellular identity and function. By comparing transcriptome and proteome, we identified mRNAs linked to B cell activation and differentiation that are expressed without detectable protein. These "poised" mRNAs might enable rapid protein production through increased translation or protein stability. In addition, we found that the translational repressor PDCD4 restrains the response of marginal zone B cells to a T-independent antigen. Our molecular characterization of B cell maturation is a valuable resource to further explore the mechanisms underpinning the specialised functions of B cell subsets.

在B细胞成熟过程中，过渡态B细胞与成熟B细胞会获得细胞内在特性，这些特性决定了它们脱离静息状态并启动有效免疫应答的能力。本研究采用高分辨率质谱技术，对小鼠脾脏来源的各B细胞亚群的蛋白质组进行定量分析，并绘制定义细胞身份与功能的环境感知因子、转录起始因子及翻译起始因子的差异表达图谱。通过对比转录组与蛋白质组数据，本研究鉴定出一批与B细胞活化及分化相关的信使RNA（mRNA），此类mRNA在转录后未检测到对应蛋白质的表达。这些"待命型"mRNA可通过增强翻译效率或提升蛋白质稳定性，实现蛋白质的快速合成。此外，本研究发现翻译抑制因子PDCD4可抑制边缘区B细胞对T细胞非依赖性抗原的应答反应。本研究对B细胞成熟过程的分子特征解析，可为进一步探究B细胞亚群特化功能的调控机制提供宝贵的研究资源。