Journal Article

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

Walden, Tomas, Guo, Feilong, Oh, Jee-Hwan, Phillipson, Mia, Sedin, John, Ahl, David, Roos, Stefan, Liu, Hao-Yu, van Pijkeren, Jan Peter, Bertilsson, Stefan, Seignez, Cedric, Giraud, Antoine, Holm, Lena

2021

Overview

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. 3CbyP5PufHSWXKDo4r3t6t Video abstract

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Antigens / Autocrine signalling / Bcl-6 protein / Bioinformatics / Biomedical and Life Sciences / Biomedicine / 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 / Medical Microbiology / Metabolism / Microbial Ecology / Microbial Genetics and Genomics / Microbiology / Microbiomes / Microbiota / Mikrobiologi / PD-1 dependent / PD-1 protein / Population / Probiotics / R2LC / Sphingosine 1-phosphate / Transcription / Virology