Distinct B cell subsets in Peyer’s patches convey probiotic effects by Limosilactobacillus reuteri

• Published in: Microbiome Vol. 9; no. 1; pp. 1 - 198
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London BioMed Central 03.10.2021; BMC
• Subjects: Antigens; Autocrine signalling; Bcl-6 protein; CCR6 protein; CD69 antigen; Cell activation; Cell cycle; Cell differentiation; Cell interactions; Cell size; Colitis; Dextran; Digestive system; Dysbacteriosis; Flow cytometry; Genes; Genotype & phenotype; Gut microbiome; Hypoxia; Immune system; Immunoglobulin A; Immunoglobulin D; Inflammation; Inflammatory bowel disease; Innate-like B lymphocytes; Intestinal microflora; Intestine; Kinases; Lymphatic system; Lymphocytes; Lymphocytes B; Metabolism; Microbiology; Microbiomes; Microbiota; Mikrobiologi; PD-1 dependent; PD-1 protein; Population; Probiotics; R2LC; Sphingosine 1-phosphate; Transcription
• ISSN: 2049-2618; 2049-2618
• DOI: 10.1186/s40168-021-01128-4

Abstract Background 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. Results 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. Conclusions 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.