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Research article - Peer-reviewed, 2021

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

Authors' information

Liu, Hao-Yu
Yangzhou University
Giraud, Antoine
Uppsala University
Seignez, Cedric
Uppsala University
Ahl, David
Uppsala University
Guo, Feilong
Uppsala University
Sedin, John
Uppsala University
Walden, Tomas
Uppsala University
Oh, Jee-Hwan
University of Wisconsin Madison
van Pijkeren, Jan Peter
University of Wisconsin Madison
Holm, Lena
Uppsala University
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Swedish University of Agricultural Sciences, Department of Aquatic Sciences and Assessment
Phillipson, Mia
Uppsala University

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