CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch

Ebisawa, Masashi; Hase, Koji; Takahashi, Daisuke; Kitamura, Hiroshi; Knoop, Kathryn A.; Williams, Ifor R.; Ohno, Hiroshi

doi:10.1093/intimm/dxq478

Cited by 54 publications

(88 citation statements)

References 26 publications

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“…In WT mice, as anticipated, dense CCL20-specific immunolabeling was detected exclusively in association with the FAE (Fig. 7A) (Kobayashi et al, 2013, Zhao et al, 2003, Ebisawa et al, 2011). Our analysis showed that c-Rel-deficiency did not significantly affect the magnitude and distribution of CCL20 protein or mRNA expression when compared to WT mice (Fig.…”

Section: Resultssupporting

confidence: 82%

c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium

et al. 2017

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M cells reside within the follicle-associated epithelium (FAE) overlying the gut-associated lymphoid tissues. These unique phagocytic epithelial cells enable the mucosal immune system to sample antigens within the lumen of the intestine. The differentiation of M cells from uncommitted precursors in the FAE is dependent on the production of receptor activator of nuclear factor-κB ligand (RANKL) by subepithelial stromal cells. The ligation of a variety of cell surface receptors activates the nuclear factor-κB (NF-κB) family of transcription factors which in-turn induce the transcription of multiple target genes. RANKL-stimulation can stimulate the nuclear translocation of the NF-κB subunit c-Rel. We therefore used c-Rel-deficient mice to determine whether the differentiation and functional maturation of M cells in the Peyer’s patches was dependent on c-Rel. Our data show that c-Rel-deficiency does not influence the expression of RANKL or RANK in Peyer’s patches, or the induction of M-cell differentiation in the FAE. RANKL-stimulation in the differentiating M cells induces the expression of SpiB which is essential for their subsequent maturation. However, SpiB expression in the FAE was also unaffected in the absence of c-Rel. As a consequence, the functional maturation of M cells was not impaired in the Peyer’s patches of c-Rel-deficient mice. Although our data showed that the specific expression of CCL20 and ubiquitin D in the FAE was not impeded in the absence of c-Rel, the expression of ubiquitin D was dramatically reduced in the B cell-follicles of c-Rel-deficient mice. Coincident with this, we also observed that the status of follicular dendritic cells in the B cell-follicles was dramatically reduced in Peyer’s patches from c-Rel-deficient mice. Taken together, our data show that c-Rel is dispensable for the RANKL-mediated differentiation and functional maturation of M cells.

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Section: Resultssupporting

confidence: 82%

c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium

et al. 2017

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“…M cells are specifically present in the FAE of GALTs and have a nonredundant role in antigen uptake and the induction of immune reactions 9,10,14 . Despite previous reports on the possible role of B cells in M cell development 34,35 , studies showed that the M cell number is not decreased even in B cell deficiency 36,37 , leaving the mechanism of M cell induction unclear. Mesenchymal stromal cells have attracted considerable attention as an important regulator of the immune system 8 , and this study shows that MCi cells, a subset of GALT-resident mesenchymal cells, control IgA responses against luminal microbes.…”

Section: Discussionmentioning

confidence: 82%

Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota

et al. 2017

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Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is dependent on microbial sampling and cellular interaction in the subepithelial dome (SED). However it is unclear how IgA induction is predominantly initiated in the SED. Here we show that previously unrecognized mesenchymal cells in the SED of GALTs regulate bacteria-specific IgA production and diversify the gut microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact with the gut epithelium to control CCL20 expression and microfold (M) cell differentiation. The deletion of mesenchymal RANKL impairs M cell-dependent antigen sampling and B cell-dendritic cell interaction in the SED, which results in a reduction in IgA production and a decrease in microbial diversity. Thus, the subepithelial mesenchymal cells that serve as M cell inducers have a fundamental role in the maintenance of intestinal immune homeostasis.

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“…CD21 lo human B cells have been proposed by some investigators to be exhausted or anergic B cells [24, 29–33]. Another study demonstrated that murine CCR6 hi CD11c int B cells were shown to promote M-cell differentiation in Peyer’s patches [34]. These data together provided an early indication that CD11c+ B cells, or their equivalents, are important in humans.…”

Section: Cd11c Expression In B Cellsmentioning

confidence: 96%

CD11c+ T-bet+ memory B cells: Immune maintenance during chronic infection and inflammation?

Winslow

Papillion

Kenderes

et al. 2017

Cellular Immunology

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CD11c+ T-bet+ B cells have now been detected and characterized in different experimental and clinical settings, in both mice and humans. Whether such cells are monolithic, or define subsets of B cells with different functions is not yet known. Our studies have identified CD11c+ IgM+ CD19hi splenic IgM memory B cells that appear at approximately three weeks post-ehrlichial infection, and persist indefinitely, during low-level chronic ehrlichial infection. Although the CD11c+T-bet+ B cells we have described are distinct, they appear to share many features with similar cells detected under diverse conditions, including viral infections, aging, and autoimmunity. We propose that CD11c+ T-bet+ B cells as a group share characteristics of memory B cells that are maintained under conditions of inflammation and/or low-level chronic antigen stimulation. In some cases, these cells may be advantageous, by providing immunity to re-infection, but in others may be deleterious, by contributing to aged-associated autoimmune responses.

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CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch

Cited by 54 publications

References 26 publications

c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium

c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium

Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota

CD11c+ T-bet+ memory B cells: Immune maintenance during chronic infection and inflammation?

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