scholarly journals Distinct B Cell Subsets in Peyer’s Patches Convey Probiotic Effects by Lactobacillus Reuteri

2021 ◽  
Author(s):  
Hao-Yu Liu ◽  
Antoine Giraud ◽  
Cedric Seignez ◽  
David Ahl ◽  
Feilong Guo ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Intestinal Microbiota ◽  
Immune Cell ◽  
Lactobacillus Reuteri ◽  
Peyer's Patches ◽  
Intestinal Microbiome ◽  
Peroral Administration ◽  
Peyer’S Patches ◽  
B Cell Subsets

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 Lactobacillus reuteri R2LC affects B lymphocytes and IgA induction in the PPs, as well as the downstream consequences on 28 intestinal microbiota and inflammation susceptibility. 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.

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

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hao-Yu Liu ◽  
Antoine Giraud ◽  
Cedric Seignez ◽  
David Ahl ◽  
Feilong Guo ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Intestinal Microbiota ◽  
Immune Cell ◽  
Peyer's Patches ◽  
Intestinal Microbiome ◽  
Peroral Administration ◽  
Peyer’S Patches ◽  
B Cell Differentiation ◽  
B Cell Subsets

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.

scholarly journals Two Distinct Pathways of B-Cell Development in Peyer’s Patches

1995 ◽  
Vol 4 (4) ◽  
pp. 263-277 ◽  
Author(s):  
Philip J. Griebel ◽  
Birgit Kugelberg ◽  
Giorgio Ferrari
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Lymphoid Tissue ◽  
Day Treatment ◽  
Cell Development ◽  
B Cell Development ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Dexamethasone Treatment

The developmental biology of sheep ileal and jejunal Peyer’s patches (PP) was investigated using corticosteroids to deplete immature B lymphocytes. During a 7-day treatment with dexamethasone, ileal PP follicular (iPf)B-cell proliferation was arrested and most iPfB-cells died. This resulted in follicular involution with the survival of mesenchymal cells. No iPfB-cell proliferation was detected in follicular remnants for 4 weeks postdexamethasone treatment, and during a subsequent 3-month period, there was limited iPfB-cell proliferation that resulted in a partial regeneration of follicles. Ileal PP involution was also associated with a severe B lymphopenia that persisted for over 14 weeks and was characterized by the survival of primarily isotype-switched and CD5+sIgM+B-cells in blood. In contrast, the size of jejunal PP follicles was reduced following dexamethasone treatment, but intrafollicular B-cell proliferation was not arrested. Furthermore, within 4 weeks, the jejunal PP follicles had recovered in size and cellularity and there was no disruption in IgA plasma-cell production. Thus, dexamethasone selectively depleted iPfB-cells and revealed that the ileal and jejunal PPs contain functionally distinct B-cell populations. The partial regeneration of the iPfB-cell population indicated that either an intrafollicular, corticosteroid-resistant B-stem cell existed or that ileal PP follicles can be repopulated by circulating B-cells. Finally, the association between ileal PP involution and the absence of circulating, CD5-B-cells confirmed that this lymphoid tissue provides an essential environment for conventional sIgM+B-cell development.

scholarly journals Dynamics of Adaptive Immune Cell and NK Cell Subsets in Patients With Ankylosing Spondylitis After IL-17A Inhibition by Secukinumab

2021 ◽  
Vol 12 ◽  
Author(s):  
Yutong Jiang ◽  
Mingcan Yang ◽  
Yanli Zhang ◽  
Yefei Huang ◽  
Jialing Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Immune Cell ◽  
Nk Cell ◽  
Wilcoxon Test ◽  
Cell Distribution ◽  
B Cell Subsets

Background: Anti-IL-17A therapy is generally effectively applied in patients with Ankylosing Spondylitis (AS) to achieve and maintain remission. However, the influence of anti-IL-17A on the composition of the immune system is not apparent. Our prospective study was to explore the changes in immune imbalance regarding T cell, B cell and natural killer (NK) cell subsets after secukinumab treatment in AS patients.Methods: Immune cell distribution of 43 AS patients treated with secukinumab for 12 weeks and 47 healthy controls (HC) were evaluated. Flow cytometry using monoclonal antibodies against 25 surface markers was accomplished to explore the frequencies of lineage subsets. The differences between HC, AS pre-treatment, and post-treatment were compared using the paired Wilcoxon test, Mann-Whitney U test, and ANOVA.Results: AS patients had altered immune cell distribution regarding T cell and B cell subsets. Apart from activated differentiation of CD4+ T cell, CD8+ T cell and B cell, higher levels of cytotoxic T (Tc) two cells and Tc17 cells were noted in AS patients. We confirmed that helper T (Th) one cell became decreased; however, Th17 cells and T follicular helper (Tfh) 17 cells went increased in AS. After 12 weeks of secukinumab therapy, CRP and ASDAS became significantly decreased, and meanwhile, the proportions of Th1 cells, Tfh17 cells and classic switched B cells were changed towards those of HC. A decreased CRP was positively correlated with a decrease in the frequency of naïve CD8+ T cells (p = 0.039) and B cells (p = 0.007) after secukinumab treatment. An elevated level of T cells at baseline was detected in patients who had a good response to secukinumab (p = 0.005).Conclusion: Our study confirmed that AS patients had significant multiple immune cell dysregulation. Anti-IL-17A therapy (Secukinumab) could reverse partial immune cell imbalance.

scholarly journals The Effect of Dosage, Gestational Age and Splenectomy on Anti-IgM Interception of Prenatal B-cell Development in Sheep

2003 ◽  
Vol 10 (1) ◽  
pp. 19-26 ◽  
Author(s):  
P. McCullagh ◽  
C. McL. Press ◽  
S. J. McClure ◽  
H. J. Larsen ◽  
T. Landsverk
Keyword(s):  
Stem Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
B Cell Depletion ◽  
Limited Period ◽  
In Pregnancy

The administration of a single bolus of anti-IgM antibody to foetal lambs early in pregnancy produces prolonged B-cell depletion. The present study investigated this depletion by examining the effect, on B-cell development in the ileal Peyer's patches, of varying the timing and dosage of antibody administration and by supplementing anti-IgM with surgical splenectomy. The capacity of a 1 mg bolus of anti-IgM to deplete Peyer's patches of B cells was lost if its administration was deferred until two thirds of the way through pregnancy, but persisted beyond this time if weight-adjusted doses were used. Splenectomy of the foetus performed at an earlier age failed to extend the age at which a 1 mg dose of antibody remained effective. As the concentration of murine immunoglobulin in foetal serum was greatly reduced after 21 days, it is inferred that ongoing suppression of B-cell development is not dependent on the continued presence of murine immunoglobulin. The enduring nature of suppression could be attributable to a limited period during which differentiation of B cells from stem cells normally occurs, although further studies will be needed to investigate this and other possible explanations for the effect of anti-IgM treatment on prenatal B-cell development in sheep.

scholarly journals Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. I. T cells derived from Peyer's patches that switch sIgM B Cells to sIgA B cells in vitro

1983 ◽  
Vol 157 (2) ◽  
pp. 433-450 ◽  
Author(s):  
H Kawanishi ◽  
LE Saltzman ◽  
W Strober
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Cell Cultures ◽  
Peyer's Patches ◽  
Lymphoid Tissues ◽  
Peyer’S Patches ◽  
Ig Synthesis

To explore mechanisms of T cell regulation governing mucosal IgA immune response, concanavalin A-induced cloned T cell lines from Peyer's patches (PP) as well as spleen were established. The cloned cell lines expressed Thy- 1.2(+), Lyt-l(+)2(-) and were radioresistant (1,500 rad). The capacity of the cloned T cells to regulate Ig synthesis was determined by measuring their effect on lipopolysaccharide (LPS)-induced polyclonal Ig synthesis by PP B cells. In initial studies Ig secreted by B cells was determined by double antibody radioimmunoassay. LPS in the absence of cloned T cells induced abundant amounts of IgM (average 8,860 ng/2 × 10(5) B cells) and IgG (average 1,190 ng/2 × 10(5) B cells), but little or no IgA. The addition of PP cloned T cells markedly suppressed production of IgM (88 percent at the highest T/B cell ratio, 4:1), but the addition of spleen cloned T cells suppressed only a little or not at all. IgG production was inhibited by both PP and spleen T clone cells (70 percent at the 4:1 T/B ratio), wheras IgA synthesis was enhanced by both clones, but only to a limited degree. In subsequent studies the expression of class-specific surface Ig (sIg) and cytoplasmic Ig (cIg) on/in unseparated PP B cells as well as Ig class- specific PP B cells and spleen B cells during culture with or without the cloned T cells was determined by immunofluorescence. The major findings were as follows: (a) Compared with unseparated B cell cultures and cultures of purified sIgM B cells derived from PP containing LPS alone, cultures containing LPS and PP cloned T cells showed a marked decrease in cIgM-, sIgG-, and cIgG-expressing cells that was accompanied by a striking increase in sIgA-bearing, but not cIgA-containing, cells. In contrast, unseparated B cell cultures and cultures of purified sIgM B cells derived from PP containing LPS and spleen cloned T cells did not show any increase in sIgA- bearing cells. (b) Compared with purified sIgG-bearing PP B cell cultures containing LPS alone, purified sIgG-bearing PP B cell cultures containing both LPS and PP cloned T cells showed no substantial change in sIgG- or cIgG- expressing cells, and no sIgA- or cIgA- expressing cells appeared. (c) Compared with sIgA-bearing PP B cell cultures containing LPS alone, purified sIgA-bearing PP B cell cultures containing both LPS and PP cloned T cells showed no increased proliferation, and cIgA cells did not occur. Cultures of purified sIgM B cells derived from spleen containing LPS and PP cloned T cells showed qualitatively similar changes. From these results we conclude that PP cloned T cells induced class-specific switching from sIgM- to sIgA- bearing B cells, whereas spleen cloned T cells lacked this property, although they may have induced an IgM {arrow} IgG or intersubclass IgG switch. These processes seem to be in part tissue dependent. Furthermore, the PP switch T cells appear to operate as true switch cells, which govern the pathway of DNA recombination events, rather than as classical helper cells, which act to expand already differentiated cells. Finally, these switch T cells probably account for the fact that PP are an important source of IgA B cells and also a major site of IgA heavy chain class switching during gut-associated mucosal B cell proliferation and differentation.

P1740KINETICS OF B-CELL SUBSETS RECONSTITUTION FOLLOWING RITUXIMAB TREATMENT IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yamei Li ◽  
Yunying Shi ◽  
Tao Lin ◽  
Xianding Wang ◽  
Lin Yan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Kidney Transplant ◽  
Cell Population ◽  
Immune Cell ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Antibody Mediated Rejection ◽  
B Cell Subsets

Abstract Background and Aims With the application of B-cell-depleting agent rituximab, plasmapheresis and powerful immunosuppression, ABO-incompatible kidney transplant recipients (ABOi-KT) have successfully overcome the ABO antibody barrier. As an important immune cell population, B cells are not only involved in antibody-mediated rejection, but also have been reported to have different immunoregulatory effects due to the existence of distinct B cell subsets. Therefore, comprehensively understanding the reconstitution of B-cell subsets in ABOi-KTRs is crucial to know the immune status that may be related to the subsequent complications. Method Fresh whole blood were collected from 22 ABOi-KTRs and 22 ABO-compatible recipients (ABOc-KTRs) at 0, 1week, 2 weeks ,1month, 3months, and 6 months post-transplantation between October 2018 and May 2019. In addition, pre-desensitization samples were also collected from ABOi-KTRs. B cell subsets including total, naïve, memory, plasma, plasma blast and regulatory B cells were determined by flow cytometry. Results The percentages of B cells in ABOi group remained extremely low and significantly lower than ABOc group through the first 6 months after rituximab treatment (Fig. A). Similar trends were observed in total memory and switched memory B cells whose frequencies increased within first 2 weeks, then decreased thereafter. Meanwhile, the significant differences between ABOi and ABOc groups disappeared at 6 months (Fig. B-D). In addition, plasma and plasma blast B cells increased 2 weeks after transplantation and were significantly higher in ABOi group compared to ABOc group (Fig. E, G), while Naïve B cells started to elevate 1 month after transplantation in ABOi-KTRs and significantly higher proportions were found in ABOc group through the entire 6 months (Fig. F). No obvious difference was observed between ABOi and ABOc groups regarding unswitched memory and regulatory B cell percentages (Fig. C, H). Conclusion Our preliminary results indicated that B-cell depletion therapy applied in ABOi-KTRs not only significantly reduced the number of B cells, but also changed the composition of B cell subsets in the remaining B cell population. Whether such alteration would be clinical significance requires further follow-up.

scholarly journals Teriflunomide treatment reduces B cells in patients with MS

2017 ◽  
Vol 4 (6) ◽  
pp. e403 ◽  
Author(s):  
Ilaria Gandoglia ◽  
Federico Ivaldi ◽  
Alice Laroni ◽  
Federica Benvenuto ◽  
Claudio Solaro ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Immune Cell ◽  
Nk Cell ◽  
Detectable Effect ◽  
Open Label ◽  
Regulatory B Cell ◽  
Cell Numbers ◽  
B Cell Subsets

Objective:To study the immunomodulatory effect of teriflunomide on innate and adaptive immune cell populations through a pilot, open-label, observational study in a cohort of patients with relapsing-remitting MS.Methods:Blood lymphocytes were isolated from 10 patients with MS before and after 3 or 12 months of treatment. Adaptive and innate immune cell subsets were analyzed by flow cytometry as follows: B cells (memory, regulatory, and mature subsets), T cells (effector and regulatory subsets), and natural killer (NK) cells (CD56dim and CD56bright subsets).Results:Our results show that teriflunomide significantly reduces absolute counts of total CD19+ B cells and mature and regulatory B-cell subsets. T cells were affected to a lesser extent, with a trend in reduction of absolute counts for both T effector CD4+ cells (Th1, Th17 and Th1/17) and T regulatory CD8+ and CD4+ cells. Teriflunomide had no detectable effect on NK-cell numbers.Conclusions:In our small cohort, teriflunomide treatment affects mainly and significantly on B-cell numbers, while having a milder effect on T-cell numbers. Larger cohorts are necessary to confirm these findings and understand the effect of teriflunomide on the functionality of these cells.

scholarly journals CD154 Costimulated Ovine Primary B Cells, a Cell Culture System That Supports Productive Infection by Bovine Leukemia Virus

2001 ◽  
Vol 75 (3) ◽  
pp. 1095-1103 ◽  
Author(s):  
A. Van den Broeke ◽  
Y. Cleuter ◽  
T. Beskorwayne ◽  
P. Kerkhofs ◽  
M. Szynal ◽  
...  
Keyword(s):  
Cell Culture ◽  
B Cells ◽  
B Cell ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Peyer's Patches ◽  
Productive Infection ◽  
Lymphoid Tissues ◽  
Peyer’S Patches

ABSTRACT Bovine leukemia virus (BLV) is closely associated with the development of B-cell leukemia and lymphoma in cattle. BLV infection has also been studied extensively in an in vivo ovine model that provides a unique system for studying B-cell leukemogenesis. There is no evidence that BLV can directly infect ovine B cells in vitro, and there are no direct data regarding the oncogenic potential of the viral Tax transactivator in B cells. Therefore, we developed ovine B-cell culture systems to study the interaction between BLV and its natural target, the B cell. In this study, we used murine CD154 (CD40 ligand) and γ-chain-common cytokines to support the growth of B cells isolated from ovine lymphoid tissues. Integrated provirus, extrachromosomal forms, and viral transcripts were detected in BLV-exposed populations of immature, rapidly dividing surface immunoglobulin M-positive B cells from sheep ileal Peyer's patches and also in activated mature B cells isolated from blood. Conclusive evidence of direct B-cell infection by BLV was obtained through the use of cloned B cells derived from sheep jejunal Peyer's patches. Finally, inoculation of sheep with BLV-infected cultures proved that infectious virus was shed from in vitro-infected B cells. Collectively, these data confirm that a variety of ovine B-cell populations can support productive infection by BLV. The development of ovine B-cell cultures permissive for BLV infection provides a controlled system for investigating B-cell leukemogenic processes and the pathogenesis of BLV infection.

scholarly journals A Single-Cell Transcriptome Profiling of Anterior Kidney Leukocytes From Nile Tilapia (Oreochromis niloticus)

2021 ◽  
Vol 12 ◽  
Author(s):  
Liting Wu ◽  
Along Gao ◽  
Lan Li ◽  
Jianlin Chen ◽  
Jun Li ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Nile Tilapia ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Transcriptome ◽  
B Cell Subsets ◽  
Single Cell Transcriptome

Teleost fish anterior kidney (AK) is an important hematopoietic organ with multifarious immune cells, which have immune functions comparable to mammalian bone marrow. Myeloid and lymphoid cells locate in the AK, but the lack of useful specific gene markers and antibody-based reagents for the cell subsets makes the identification of the different cell types difficult. Single-cell transcriptome sequencing enables single-cell capture and individual library construction, making the study on the immune cell heterogeneity of teleost fish AK possible. In this study, we examined the transcriptional patterns of 11,388 AK leukocytes using 10× Genomics single-cell RNA sequencing (scRNA-seq). A total of 22 clusters corresponding to five distinct immune cell subsets were identified, which included B cells, T cells, granulocytes, macrophages, and dendritic cells (DCs). However, the subsets of myeloid cells (granulocytes, macrophages, and DCs) were not identified in more detail according to the known specific markers, even though significant differences existed among the clusters. Thereafter, we highlighted the B-cell subsets and identified them as pro/pre B cells, immature/mature B cells, activated B/plasmablasts, or plasma cells based on the different expressions of the transcription factors (TFs) and cytokines. Clustering of the differentially modulated genes by pseudo-temporal trajectory analysis of the B-cell subsets showed the distinct kinetics of the responses of TFs to cell conversion. Moreover, we classified the T cells and discovered that CD3+CD4−CD8−, CD3+CD4+CD8+, CD4+CD8−, and CD4−CD8+ T cells existed in AK, but neither CD4+CD8− nor CD4−CD8+ T cells can be further classified into subsets based on the known TFs and cytokines. Pseudotemporal analysis demonstrated that CD4+CD8− and CD4−CD8+ T cells belonged to different states with various TFs that might control their differentiation. The data obtained above provide a valuable and detailed resource for uncovering the leukocyte subsets in Nile tilapia AK, as well as more potential markers for identifying the myeloid and lymphoid cell types.

scholarly journals CXCR4 promotes B cell egress from Peyer’s patches

2013 ◽  
Vol 210 (6) ◽  
pp. 1099-1107 ◽  
Author(s):  
Timothy H. Schmidt ◽  
Oliver Bannard ◽  
Elizabeth E. Gray ◽  
Jason G. Cyster
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peyer's Patches ◽  
Lymphoid Tissues ◽  
Peyer’S Patches ◽  
Lymphatic Endothelial Cells ◽  
Cell Passage ◽  
Wild Type ◽  
Cell Responses ◽  
Mixed Chimeras

Peyer’s patches (PPs) play a central role in supporting B cell responses against intestinal antigens, yet the factors controlling B cell passage through these mucosal lymphoid tissues are incompletely understood. We report that, in mixed chimeras, CXCR4-deficient B cells accumulate in PPs compared with their representation in other lymphoid tissues. CXCR4-deficient B cells egress from PPs more slowly than wild-type cells, whereas CXCR5-deficient cells egress more rapidly. The CXCR4 ligand, CXCL12, is expressed by cells adjacent to lymphatic endothelial cells in a zone that abuts but minimally overlaps with the CXCL13+ follicle. CXCR4-deficient B cells show reduced localization to these CXCL12+ perilymphatic zones, whereas CXCR5-deficient B cells preferentially localize in these regions. By photoconverting KikGR-expressing cells within surgically exposed PPs, we provide evidence that naive B cells transit PPs with an approximate residency half-life of 10 h. When CXCR4 is lacking, KikGR+ B cells show a delay in PP egress. In summary, we identify a CXCL12hi perilymphatic zone in PPs that plays a role in overcoming CXCL13-mediated retention to promote B cell egress from these gut-associated lymphoid tissues.

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