PDF(Pubmed)
Abstract：
B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods (\"per gene\" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/PMAIP1, the brain expressed X-linked 2/BEX2 gene and the B cell Fas apoptotic inhibitory molecule/FAIM, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocyte-derived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination.
摘要：
B细胞转录组特征有望早期预测疫苗诱导的体液免疫和疫苗保护功效。我们在三剂MMR（MR3）疫苗之前/之后对232名健康成人参与者进行了纵向研究。我们使用两种分析方法（“每个基因”线性模型和联合分析）评估了纯化B细胞的基线和早期转录模式及其与MMR疫苗接种后麻疹特异性体液免疫的关联。我们的研究确定了与麻疹特异性中和抗体滴度和/或结合抗体滴度相关的MMR3后不同的早期转录特征/基因。最重要的基因包括：白介素20受体亚基β/IL20RB基因（IL-24的亚基受体，一种参与生发中心B细胞成熟/反应的细胞因子）；佛波醇-12-肉豆蔻酸酯-13-乙酸酯诱导的蛋白1/PMAIP1，大脑表达X连接的2/BEX2基因和B细胞Fas凋亡抑制分子/FAIM，参与高亲和力B细胞克隆的选择和凋亡/凋亡的调节;以及IL16（编码CD4的B淋巴细胞衍生的IL-16配体），参与B细胞之间的串扰，树突状细胞和辅助性T细胞。显著富集的途径包括B细胞信号转导，凋亡/凋亡调节，代谢途径，细胞周期相关通路，以及与病毒感染相关的途径，在其他人中。总之,我们的研究确定了与抗原诱导的B细胞增殖相关的基因/途径，分化,凋亡，和克隆选择，与之相关的，并影响MMR疫苗接种后麻疹病毒特异性体液免疫。
