Commensal microbes drive the generation of large numbers of bone marrow plasma cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE87091 | GEO | 2018/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:Gut-educated IgA-secreting plasma cells that disseminate beyond the mucosa and into systemic tissues can help prevent disease in several contexts. Here we show, the commensal bacteria Bacteroides fragilis (Bf), is an efficient inducer of systemic IgA responses. The generation of bone marrow IgA plasma cells and high levels of serum IgA specific to Bf requires robust intestinal colonization. Bf-specific IgA responses were severely diminished in mice lacking Peyer’s patches, but not mice lacking a cecal patch. Colonization resulted in few changes in the host transcriptional profile in the gut, suggesting a commensal relationship. High levels of Bf-specific serum IgA, but not IgG, provided protection from peritoneal abscess formation in a bowel perforation model of Bf dissemination. These findings demonstrate a critical role for bacterial colonization and Peyer’s patches in the induction of robust systemic IgA responses that confer protection from bacterial dissemination originating from the gut.
2024-07-25 | GSE272717 | GEO
Project description:Induction of adaptive immune responses to commensal microbes is critical for intestinal homeostasis, and perturbation of these responses is associated with multiple chronic inflammatory disorders. However, the mechanisms underlying the induction and regulation of mucosal B cells targeting commensal microbes remain poorly understood, in part due to a lack of tools to identify commensal-specific B cells ex vivo. To address this, we first sought to identify immunodominant protein epitopes recognized by Segmented Filamentous Bacteria (SFB) specific serum antibodies using a whole-genome phage display screen and identified immunogenic proteins engaging IgA, IgG1 and IgG2b responses. Using these antigens, we generated B cell tetramers to identify and track SFB-specific B cell responses in the gut associated lymphoid tissue during natural and de novo colonization. We identified a compartmentalized response in B cell activation between Peyer’s patches and mesenteric lymph nodes, with a gradient of IgA, IgG1 and IgG2b isotypes along the small intestine, and selective production of IgG2b with the mesenteric lymph node chain. VDJ sequencing analyses and generation of SFB-specific monoclonal antibodies identified that somatic hypermutation drives affinity maturation to SFB derived antigens under homeostatic conditions. By combining phage display screening and B cell tetramer technologies, we now enable antigen-level based studies of immunity to intestinal microbes, which will advance our understanding of the ontogeny and function of commensal-specific B cell responses in tissue immunity, inflammation and repair.
2024-04-10 | GSE245084 | GEO
Project description:Plasma cells are key components of humoral immunity by secreting antibodies and providing protection against pathogens. These cells can be of IgM, IgA, or IgG subclass and migrate to class-specific niches. Localization and rareness of plasma cells make it challenge to define subclass-specific molecular hallmarks. Here, we describe how in-vitro differentiation of peripheral B-cells results in antibody-secreting plasma cells. Using a single-cell multi-modal sequencing approach (RAID) we find subclass-specific hallmark transcriptional profiles, surface protein expression and signaling pathway activation.
2023-01-02 | GSE189953 | GEO
Project description:The CD19 positive antibody secreting cells (ASC) in both bone marrow (BM) have the capacity to provide immune memory in addition to cells traditionally considered long-lived, the CD19-negative BM ASC. We performed flow cytometry (FCM) immunophenotyping, fluorescence-activated cell sorting (FACS) for cell subset isolation, ELISpot assays detecting the isotype of antibody secretion as well as antibodies against vaccine derived antigens, and comparative gene expression analyses of CD19- ASC, CD19+ ASC, CD20- B cells, and CD20+ B cells from BM. The findings may aid in the understanding of the differential cell subsets created through vaccination and lead to improved vaccine strategies and production. FACS sorted tissue B cells and antibody secreting cell subset gene expression.
2018-12-03 | GSE107683 | GEO
Project description:The mammalian gut is inhabited by a large and complex microbial community that lives in a mutualistic relationship with its host. Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with this commensal microbiota. Secretory antibodies are generated from the active polymeric Ig receptor (pIgR)-mediated transport of IgA and IgM antibodies to the gut lumen and form the first line of adaptive immune defense of the intestinal mucosa. We probed mucosal homeostasis in pIgR knockout (KO) mice, which lack secretory antibodies. We found that in pIgR KO mice, colonic epithelial cells, the cell type most closely in contact with intestinal microbes, differentially expressed (>2-fold change) more than 200 genes compared with wild type mice, and upregulated the expression of anti-microbial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and wild type mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis, and that this was driven by their conventional intestinal microbiota. In conclusion, secretory antibodies or the pIgR itself are required to maintain a stable commensal microbiota. In the absence of these humoral effector components, gut homeostasis is disturbed and the outcome of colitis significantly worsened.
2013-12-28 | GSE34630 | GEO
Project description:The mammalian gut is inhabited by a large and complex microbial community that lives in a mutualistic relationship with its host. Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with this commensal microbiota. Secretory antibodies are generated from the active polymeric Ig receptor (pIgR)-mediated transport of IgA and IgM antibodies to the gut lumen and form the first line of adaptive immune defense of the intestinal mucosa. We probed mucosal homeostasis in pIgR knockout (KO) mice, which lack secretory antibodies. We found that in pIgR KO mice, colonic epithelial cells, the cell type most closely in contact with intestinal microbes, differentially expressed (>2-fold change) more than 200 genes compared with wild type mice, and upregulated the expression of anti-microbial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and wild type mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis, and that this was driven by their conventional intestinal microbiota. In conclusion, secretory antibodies or the pIgR itself are required to maintain a stable commensal microbiota. In the absence of these humoral effector components, gut homeostasis is disturbed and the outcome of colitis significantly worsened. 4 groups: wild type mice treated with antibiotic (5 replicates), wild type mice left untreated (5 replicates), pIgR KO mice treated with antibiotic (6 replicates), and pIgR KO mice left untreated (6 replicates).
2013-12-28 | E-GEOD-34630 | biostudies-arrayexpress
Project description:B-lymphocytes constitute an important aspect of mammalian immune systems by virtue of their ability to produce highly specific antibodies in response to foreign antigens and pathogens. When B-lymphocytes encounter the particular antigen that they are responsive to, they differentiate into two types of cells: short-lived antibody-secreting plasma cells and long-lived memory cells. While the plasma B cells are responsible for the rapid resolution of a current infection or immune challenge, the memory B cells are responsible for mounting a rapid response to subsequent exposures. Previous work had demonstrated that treatment of mice with a single dose of anti-CD40 at the time of immunization leads to improved secondary responses, suggesting an enhancement of the memory B cell pool. We are currently studying the molecular mechanisms underlying the generation of memory B cells, using CD40 signalling as a tool. We have carried out a microarray analysis of genome-wide gene expression patterns in naïve B-lymphocytes following CD40 signalling over multiple time points.
2012-12-25 | GSE29950 | GEO
Project description:Nasal vaccination elicits a humoral immune response that provides protection from airborne pathogens, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways remain unknown. Here, we define glandular acinus structures of the nasal turbinates as an immunological niche that recruits IgA-secreting plasma cells from the nasal-associated lymphoid tissues (NALT) in response to intranasal vaccination. Using intact organ imaging, we investigated the cellular events that support antibody-mediated immune responses in the mouse upper airways. Through visualization of antigen-specific T and B cells in the upper airways, we demonstrate that nasal vaccination induced extensive B cell expansion in the subepithelial dome (SED) of the NALT, followed by invasion into commensal bacteria-driven chronic germinal centers (GCs) in a T cell-dependent manner. Antigen-specific B cell response in the NALT required pre-expansion of cognate T cells, which initiate the immune response in the inter-follicular regions of the NALT, and occurred effectively in the presence of Monophosphoryl-Lipid A (MPLA), a synthetic, non-toxic TLR-4 agonist. NALT ablation and blockade of PSGL-1 demonstrated that intranasal vaccination generates IgA+ plasma cells that home to the nasal turbinates through the blood circulation where they are positioned primarily around glandular acinus structures. Thus, the glandular part of the nasal turbinate is an immunological niche that hosts NALT-derived IgA-secreting cells. These cellular events can be manipulated to design vaccines against inhaled pathogens or in the treatment of upper airway allergic responses.
2024-05-30 | GSE252018 | GEO
Project description:Nasal vaccination elicits a humoral immune response that provides protection from airborne pathogens, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways remain unknown. Here, we define glandular acinus structures of the nasal turbinates as an immunological niche that recruits IgA-secreting plasma cells from the nasal-associated lymphoid tissues (NALT) in response to intranasal vaccination. Using intact organ imaging, we investigated the cellular events that support antibody-mediated immune responses in the mouse upper airways. Through visualization of antigen-specific T and B cells in the upperairways, we demonstrate that nasal vaccination induced extensive B cell expansion in the subepithelial dome (SED) of the NALT, followed by invasion into commensal bacteria-driven chronic germinal centers (GCs) in a T cell-dependent manner. Antigen-specific B cell response in the NALT required pre-expansion of cognate T cells, which initiate the immune response in the inter-follicular regions of the NALT, and occurred effectively in the presence of Monophosphoryl-Lipid A (MPLA), a synthetic, non-toxic TLR-4 agonist. NALT ablation and blockade of PSGL-1 demonstrated that intranasal vaccination generates IgA+ plasma cells that home to the nasal turbinates through the blood circulation where they are positioned primarily around glandular acinus structures. Thus, the glandular part of the nasal turbinate is an immunological niche that hosts NALT-derived IgA-secreting cells. These cellular events can be manipulated to design vaccines against inhaled pathogens or in the treatment of upper airway allergic responses.
2024-08-17 | GSE264641 | GEO
Project description:Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASC) to long-lived plasma cells (LLPC). We provide single cell transcriptional resolution of 17,347 BM ASC from 5 healthy adults. Fifteen clusters were identified ranging from newly minted ASC (cluster 1) expressing MKI67 and high MHC Class II that progressed to late clusters 5-8 through intermediate clusters 2-4. Additional clusters included IgM-predominant ASC of likely extra-follicular origin; IFN-responsive; and high mitochondrial activity ASC. Late ASCs were distinguished by differences in G2M checkpoints, MTOR signaling, distinct metabolic pathways, CD38 expression, and utilization of TNF-receptor superfamily members. They mature through two distinct paths differentiated by the degree of TNF signaling through NFKB. This study provides the first single cell resolution atlas and molecular roadmap of LLPC maturation, thereby providing insight into differentiation trajectories and molecular regulation of these essential processes in the human BM microniche. This information enables investigation of the origin of protective and pathogenic antibodies in multiple diseases and development of new strategies targeted to the enhancement or depletion of the corresponding ASC.
2023-06-28 | GSE230690 | GEO