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Research article2021Peer reviewedOpen access

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

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


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 TGF beta-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.


Innate-like B lymphocytes; Inflammatory bowel disease; Gut microbiome; PD-1 dependent; Probiotics; R2LC

Published in

2021, Volume: 9, number: 1, article number: 198
Publisher: BMC