Abstract:
An estimated quarter of the human world population is infected with gastrointestinal helminths causing major socioeconomic problems in endemic countries. A better understanding of humoral immune responses against helminths is urgently needed to develop effective vaccination strategies. Here, we used a fate mapping (FM) approach to mark germinal center (GC) B cells and their developmental fates by induced expression of a fluorescent protein during infection of mice with the helminth Nippostrongylus brasiliensis. We could show that FM+ cells persist weeks after clearance of the primary infection mainly as CD80+CD73+PD-L2+ memory B cells. A secondary infection elicited expansion of helminth-specific memory B cells and plasma cells (PCs). Adoptive transfers and analysis of somatic mutations in immunoglobulin genes further revealed that FM+ B cells rapidly convert to PCs rather than participating again in a GC reaction. These results provide new insights in the population dynamics of the humoral immune response against helminths.
摘要:
据估计,全球四分之一的人口感染了胃肠道蠕虫,在流行国家引起了重大的社会经济问题。迫切需要更好地了解针对蠕虫的体液免疫反应,以开发有效的疫苗接种策略。这里,我们使用命运作图(FM)方法通过在蠕虫感染小鼠期间诱导荧光蛋白的表达来标记生发中心(GC)B细胞及其发育命运。我们可以显示FM+细胞在原发感染清除后持续数周,主要为CD80+CD73+PD-L2+记忆B细胞。继发感染引起蠕虫特异性记忆B细胞和浆细胞(PC)的扩增。免疫球蛋白基因中体细胞突变的过继转移和分析进一步表明,FMB细胞迅速转化为PC,而不是再次参与GC反应。这些结果为针对蠕虫的体液免疫反应的种群动态提供了新的见解。