Wiarda Jayne E, Shircliff Adrienne L, Becker Sage R, Stasko Judith B, Sivasankaran Sathesh K, Ackermann Mark R, Loving Crystal L
Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA; Oak Ridge Institute for Science and Education, Agricultural Research Service Participation Program, Oak Ridge, TN, USA.
Microscopy Services Laboratory, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA.
Mucosal Immunol. 2024 Dec;17(6):1222-1241. doi: 10.1016/j.mucimm.2024.08.005. Epub 2024 Aug 13.
Peyer's patches (PPs) are B cell-rich sites of intestinal immune induction, yet PP-associated B cell signaling, activation, and differentiation are poorly defined. Single-cell and spatial transcriptomics were completed to study B cells from porcine jejunum and ileum containing PPs. Intestinal locations had distinct immune landscapes, including more follicular B cells in ileum and increased MHC-II-encoding gene expression in jejunal B cells. Despite distinct landscapes, conserved B cell dynamics were detected across intestinal locations, including B cell signaling to CD4 macrophages that are putative phagocytic, cytotoxic, effector cells and deduced routes of B cell activation/differentiation, including resting B cells migrating into follicles to replicate/divide or differentiate into antibody-secreting cells residing in intestinal crypts. A six-biomarker panel recapitulated transcriptomics findings of B cell phenotypes, frequencies, and spatial locations via ex vivo and in situ staining. Findings convey conserved B cell dynamics across intestinal locations containing PPs, despite location-specific immune environments. Results establish a benchmark of B cell dynamics for understanding intestinal immune induction important to promoting gut/overall health.
派尔集合淋巴结(PPs)是肠道免疫诱导中富含B细胞的部位,但与PP相关的B细胞信号传导、激活和分化仍不清楚。我们完成了单细胞和空间转录组学研究,以分析来自含有PPs的猪空肠和回肠的B细胞。肠道不同位置具有独特的免疫格局,包括回肠中有更多的滤泡B细胞,以及空肠B细胞中MHC-II编码基因表达增加。尽管格局不同,但在肠道不同位置检测到了保守的B细胞动态变化,包括B细胞向CD4巨噬细胞的信号传导,这些巨噬细胞被认为是吞噬性、细胞毒性效应细胞,以及推测的B细胞激活/分化途径,包括静息B细胞迁移到滤泡中进行复制/分裂或分化为驻留在肠隐窝中的抗体分泌细胞。一个包含六种生物标志物的组合通过体外和原位染色概括了B细胞表型、频率和空间位置的转录组学研究结果。研究结果表明,尽管存在位置特异性免疫环境,但在含有PPs的肠道不同位置,B细胞动态变化具有保守性。这些结果建立了一个B细胞动态变化的基准,有助于理解对促进肠道/整体健康至关重要的肠道免疫诱导过程。