Impairment of splenic IgM-memory but not switched-memory B cells in a patient with celiac disease and splenic atrophy

Sabatino, Antonio Di; Rosado, M. Manuela; Miele, Luca; Capolunghi, Federica; Cazzola, P.; Biancheri, Paolo; Carsetti, Rita; Gasbarrini, Giovanni

doi:10.1016/j.jaci.2007.07.054

Cited by 16 publications

(10 citation statements)

References 10 publications

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“…However, the role of the spleen in the defence against Ags from the gut has not been studied in detail. Nevertheless, it is known that gastrointestinal disorders such as coeliac disease or inflammatory bowel disease are associated with splenic dysfunction or cell activation [ 19 , 39 , 40 ]. The gut Ags are taken up by intestinal epithelial cells, macrophages or DCs in the intestinal mucosa.…”

Section: Discussionmentioning

confidence: 99%

Participation of the spleen in the IgA immune response in the gut

et al. 2018

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The role of the spleen in the induction of an immune response to orally administered antigens is still under discussion. Although it is well known that after oral antigen administration specific germinal centres are not only formed in the Peyers patches (PP) and the mesenteric lymph nodes (mLN) but also in the spleen, there is still a lack of functional data showing a direct involvement of splenic B cells in an IgA immune response in the gut. In addition, after removal of mLN a high level of IgA+ B cells was observed in the gut. Therefore, in this study we analysed the role of the spleen in the induction of IgA+ B cells in the gut after mice were orally challenged with antigens. Here we have shown that antigen specific splenic IgM+ B cells after in vitro antigen stimulation as well as oral immunisation of donor mice were able to migrate into the gut of recipient mice, where they predominantly switch to IgA+ plasma cells. Furthermore, stimulation of recipient mice by orally administered antigens enhanced the migration of the splenic B cells into the gut as well as their switch to IgA+ plasma cells. Removal of the mLN led to a higher activation level of the splenic B cells. Altogether, our results imply that splenic IgM+ B cells migrate in the intestinal lamina propria, where they differentiate into IgA+ plasma cells and subsequently proliferate. In conclusion, we demonstrated that the spleen plays a major role in the gut immune response serving as a reservoir of immune cells that migrate to the site of antigen entrance.

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Section: Discussionmentioning

confidence: 99%

Participation of the spleen in the IgA immune response in the gut

et al. 2018

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“…The underlying cause of this intriguing abnormality remains to be elucidated. It is possible that splenic dysfunction in patients may disrupt the anatomical sites necessary for the development and/or survival of UM B cells, as has been reported in patients with Crohn’s disease and celiac disease [ 71 , 72 ]. Alternatively, alterations in B-cell receptor signaling or other pathways may favor their differentiation into other cell fates at the expense of the IgD + CD27 + pathway [ 73 ].…”

Section: Reviewmentioning

confidence: 99%

Polychromatic flow cytometry in evaluating rheumatic disease patients

Wei¹,

Jenks²,

Sanz³

2015

Arthritis Res Ther

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B cells are central players in multiple autoimmune rheumatic diseases as a result of the imbalance between pathogenic and protective B-cell functions, which are presumably mediated by distinct populations. Yet the functional role of different B-cell populations and the contribution of specific subsets to disease pathogenesis remain to be fully understood owing to a large extent to the use of pauci-color flow cytometry. Despite its limitations, this approach has been instrumental in providing a global picture of multiple B-cell abnormalities in multiple human rheumatic diseases, more prominently systemic lupus erythematosus, rheumatoid arthritis and Sjogren’s syndrome. Accordingly, these studies represent the focus of this review. In addition, we also discuss the added value of tapping into the potential of polychromatic flow cytometry to unravel a higher level of B-cell heterogeneity, provide a more nuanced view of B-cell abnormalities in disease and create the foundation for a precise understanding of functional division of labor among the different phenotypic subsets. State-of-the-art polychromatic flow cytometry and novel multidimensional analytical approaches hold tremendous promise for our understanding of disease pathogenesis, the generation of disease biomarkers, patient stratification and personalized therapeutic approaches.

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“…In patients with common variable immunodeficiency, those presenting with recurrent infection of the respiratory tract and chronic lung disease have an extremely low frequency of IgM memory B-cells and do not produce anti-polysaccharide IgM [96,97]. Splenic dysfunction may also occur in patients with sickle cell anaemia [98], inflammatory bowel disease [99] or celiac disease [100], where both impaired IgM production by MZ B-cells and reduced phagocytosis of opsonised particles prevent the clearance of encapsulated bacteria.…”

Section: Review and Conclusionmentioning

confidence: 99%

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond

et al. 2012

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The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories — the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells — plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40+ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express “Pathogen Recognition Receptors” such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology.

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Impairment of splenic IgM-memory but not switched-memory B cells in a patient with celiac disease and splenic atrophy

Cited by 16 publications

References 10 publications

Participation of the spleen in the IgA immune response in the gut

Participation of the spleen in the IgA immune response in the gut

Polychromatic flow cytometry in evaluating rheumatic disease patients

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond

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