Liu Hao-Yu, Giraud Antoine, Seignez Cedric, Ahl David, Guo Feilong, Sedin John, Walden Tomas, Oh Jee-Hwan, van Pijkeren Jan Peter, Holm Lena, Roos Stefan, Bertilsson Stefan, Phillipson Mia
Laboratory of Animal Physiology and Molecular Nutrition, College of Animal Science and Technology, Yangzhou University, 225009, Yangzhou, PR China.
Department of Medical Cell Biology, Uppsala University, PO box 571, 75123, Uppsala, Sweden.
Microbiome. 2021 Oct 3;9(1):198. doi: 10.1186/s40168-021-01128-4.
Intestinal Peyer's patches (PPs) form unique niches for bacteria-immune cell interactions that direct host immunity and shape the microbiome. Here we investigate how peroral administration of probiotic bacterium Limosilactobacillus reuteri R2LC affects B lymphocytes and IgA induction in the PPs, as well as the downstream consequences on intestinal microbiota and susceptibility to inflammation.
The B cells of PPs were separated by size to circumvent activation-dependent cell identification biases due to dynamic expression of markers, which resulted in two phenotypically, transcriptionally, and spatially distinct subsets: small IgD/GL7/S1PR1/Bcl6, CCR6-expressing pre-germinal center (GC)-like B cells with innate-like functions located subepithelially, and large GL7/S1PR1/Ki67/Bcl6, CD69-expressing B cells with strong metabolic activity found in the GC. Peroral L. reuteri administration expanded both B cell subsets and enhanced the innate-like properties of pre-GC-like B cells while retaining them in the sub-epithelial compartment by increased sphingosine-1-phosphate/S1PR1 signaling. Furthermore, L. reuteri promoted GC-like B cell differentiation, which involved expansion of the GC area and autocrine TGFβ-1 activation. Consequently, PD-1-T follicular helper cell-dependent IgA induction and production was increased by L. reuteri, which shifted the intestinal microbiome and protected against dextran-sulfate-sodium induced colitis and dysbiosis.
The Peyer's patches sense, enhance and transmit probiotic signals by increasing the numbers and effector functions of distinct B cell subsets, resulting in increased IgA production, altered intestinal microbiota, and protection against inflammation. Video abstract.
肠道派尔集合淋巴结（PPs）形成了细菌与免疫细胞相互作用的独特微环境，这种相互作用指导宿主免疫并塑造微生物群。在此，我们研究口服益生菌罗伊氏乳杆菌R2LC如何影响PPs中的B淋巴细胞和IgA诱导，以及对肠道微生物群的下游影响和对炎症的易感性。
根据大小分离PPs中的B细胞，以规避由于标志物动态表达导致的激活依赖性细胞识别偏差，这产生了两个在表型、转录和空间上不同的亚群：小的IgD/GL7/S1PR1/Bcl6、表达CCR6的前生发中心（GC）样B细胞，具有类似先天免疫的功能，位于上皮下；大的GL7/S1PR1/Ki67/Bcl6、表达CD69的B细胞，具有很强的代谢活性，存在于GC中。口服罗伊氏乳杆菌可扩大这两个B细胞亚群，并增强前GC样B细胞的先天样特性，同时通过增加鞘氨醇-1-磷酸/S1PR1信号传导将它们保留在上皮下隔室中。此外，罗伊氏乳杆菌促进GC样B细胞分化，这涉及GC区域的扩大和自分泌TGFβ-1的激活。因此，罗伊氏乳杆菌增加了PD-1-T滤泡辅助细胞依赖性IgA的诱导和产生，这改变了肠道微生物群，并预防了葡聚糖硫酸钠诱导的结肠炎和生态失调。
派尔集合淋巴结通过增加不同B细胞亚群的数量和效应功能来感知、增强和传递益生菌信号，从而导致IgA产生增加、肠道微生物群改变以及对炎症的保护作用。视频摘要。
