scholarly journals Antibody secreting cells are critically dependent on integrin α4β7/MAdCAM-1 for intestinal recruitment and control of the microbiota during chronic colitis

2021 ◽  
Author(s):  
Christopher J. Tyler ◽  
Mauricio Guzman ◽  
Luke R. Lundborg ◽  
Shaila Yeasmin ◽  
Nadia Zgajnar ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Microbiota Composition ◽  
Chronic Colitis ◽  
Inflammatory Conditions ◽  
Expression Activity ◽  
Inflammatory Bowel ◽  
And Control ◽  
Antibody Secreting Cells

AbstractT and B cells employ integrin α4β7 to migrate to intestine under homeostatic conditions. Whether those cells differentially rely on α4β7 for homing during inflammatory conditions has not been fully examined. This may have implications for our understanding of the mode of action of anti-integrin therapies in inflammatory bowel disease (IBD). Here, we examined the role of α4β7 integrin during chronic colitis using IL-10−/− mice, β7-deficient IL-10−/−, IgA-deficient IL-10−/− mice, and antibody blockade of MAdCAM-1. We found that α4β7 was predominantly expressed by B cells. β7 deficiency and MAdCAM-1 blockade specifically depleted antibody secreting cells (ASC) (not T cells) from the colonic LP, leading to a fecal pan-immunoglobulin deficit, severe colitis, and alterations of microbiota composition. Colitis was not due to defective regulation, as dendritic cells (DC), regulatory T cells, retinaldehyde dehydrogenase (RALDH) expression, activity, and regulatory T/B-cell cytokines were all comparable between the strains/treatment. Finally, an IgA deficit closely recapitulated the clinical phenotype and altered microbiota composition of β7-deficient IL-10−/− mice. Thus, a luminal IgA deficit contributes to accelerated colitis in the β7-deficient state. Given the critical/nonredundant dependence of IgA ASC on α4β7:MAdCAM-1 for intestinal homing, B cells may represent unappreciated targets of anti-integrin therapies.

scholarly journals B cells and HSV-specific antibodies respond to HSV-2 reactivation in skin

2020 ◽  
Author(s):  
Emily S. Ford ◽  
Anton M. Sholukh ◽  
RuthMabel Boytz ◽  
Savanna S. Carmack ◽  
Alexis Klock ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Viral Infections ◽  
Specific Antibodies ◽  
Control And Prevention ◽  
Skin Biopsies ◽  
Unaffected Skin ◽  
Inflammatory Infiltrates ◽  
Antibody Secreting Cells

AbstractTissue-based T cells increasingly have been shown to be important effectors in the control and prevention of mucosal viral infections – less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in skin biopsies of persons with symptomatic HSV-2 reactivation. CD20+ B cells are observed in inflammatory infiltrates at greatest density at the time of symptomatic reactivation; HSV-2-specific antibodies to HSV-2 surface antigens are also detected. The concentrations of HSV-2-specific antibodies in tissue biopsies vary over the course of HSV-2 reactivation and healing, unlike serum where concentrations remain static over time. B cells and HSV-specific antibody were rarely present in biopsies of unaffected skin. Investigation of serial biopsies over the course of lesion healing suggests that B cells follow a more migratory than resident pattern of infiltration in HSV-affected genital skin, in contrast to T cells. Together, these observations may suggest a functional and distinct role of tissue-based B cells in the local immune response to HSV-2.

scholarly journals Induction of autoreactive B cells allows priming of autoreactive T cells.

1991 ◽  
Vol 173 (6) ◽  
pp. 1433-1439 ◽  
Author(s):  
R H Lin ◽  
M J Mamula ◽  
J A Hardin ◽  
C A Janeway
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cytochrome C ◽  
Autoantibody Production ◽  
Autoreactive T Cells ◽  
Human Cytochrome ◽  
Self Tolerance ◽  
Human Cytochrome C

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.

Immunohistochemical Study of Presence of T Cells, B Cells, and Macrophages in Periradicular Lesions of Primary Teeth

2008 ◽  
Vol 32 (4) ◽  
pp. 287-293 ◽  
Author(s):  
Michele Bolan ◽  
Daniele de Almeida Lima ◽  
Cláudia Pinto Figueiredo ◽  
Gabriella Di Giunta ◽  
Maria José de Carvalho Rocha
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Primary Teeth ◽  
Microscopic Analysis ◽  
Inflammatory Cells ◽  
Periapical Lesions ◽  
Inflammatory Processes ◽  
Local Inflammatory Reaction

BACKGROUND: The periapical lesion is the result of a local inflammatory reaction caused by bacteria and its products present on the root canal. The interaction between inflammatory cells and bacteria elicit both specific and non-specific immune responses. OBJETIVE: Due to the lack of studies evaluating the role of the immune system in periapical lesions of primary teeth and considering the potentially systemic effects that these infections can cause in children, especially because of the immaturity of their immune system, we sought to evaluate the presence of T cells, B cells and macrophages on periradicular lesions in primary teeth. STUDY DESIGN: 14 periradicular lesions were analyzed. The immunohistochemistry technique was performed using CD45RO, CD20, CD68 monoclonal antibodies aiming to identify T cells, B cells and macrophages, respectively. Cells were quantified by microscopic analysis of histological sections. RESULTS: Mean percentage of positive cells CD45RO was 11.76; CD20 was 5.25; CD68 was 10.92. Our results showed that T and B cells and macrophages comprise the majority of the inflammatory infiltrate. CONCLUSION: We concluded that both humoral and cell mediated immune reactions take place in periradicular lesions of primary teeth. The immune system plays an important role on the periradicular inflammatory processes in primary teeth.

scholarly journals Tertiary Lymphoid Structures as a Predictive Biomarker of Response to Cancer Immunotherapies

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Trüb ◽  
Alfred Zippelius
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Tumour Response ◽  
Predictive Biomarker ◽  
Exciting Field ◽  
Inflammatory Conditions ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures ◽  
Cancer Immunotherapies

Tertiary lymphoid structures (TLS) are ectopic lymphoid formations which are formed under long-lasting inflammatory conditions, including tumours. TLS are composed predominantly of B cells, T cells and dendritic cells, and display various levels of organisation, from locally concentrated aggregates of immune cells, through clearly defined B cell follicles to mature follicles containing germinal centres. Their presence has been strongly associated with improved survival and clinical outcome upon cancer immunotherapies for patients with solid tumours, indicating potential for TLS to be used as a prognostic and predictive factor. Although signals involved in TLS generation and main cellular components of TLS have been extensively characterised, the exact mechanism by which TLS contribute to the anti-tumour response remain unclear. Here, we summarise the most recent development in our understanding of their role in cancer and in particular in the response to cancer immunotherapy. Deciphering the relationship between B cells and T cells found in TLS is a highly exciting field of investigation, with the potential to lead to novel, B-cell focused immunotherapies.

scholarly journals Early Reconstitution of Antibody Secreting Cells after Allogeneic Stem Cell Transplantation

2022 ◽  
Vol 11 (1) ◽  
pp. 270
Author(s):  
Martina Hinterleitner ◽  
Clemens Hinterleitner ◽  
Elke Malenke ◽  
Birgit Federmann ◽  
Ursula Holzer ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Antibody Secreting Cells

Immune cell reconstitution after stem cell transplantation is allocated over several stages. Whereas cells mediating innate immunity recover rapidly, adaptive immune cells, including T and B cells, recover slowly over several months. In this study we investigated kinetics and reconstitution of de novo B cell formation in patients receiving CD3 and CD19 depleted haploidentical stem cell transplantation with additional in vivo T cell depletion with monoclonal anti-CD3 antibody. This model enables a detailed in vivo evaluation of hierarchy and attribution of defined lymphocyte populations without skewing by mTOR- or NFAT-inhibitors. As expected CD3+ T cells and their subsets had delayed reconstitution (<100 cells/μL at day +90). Well defined CD19+ B lymphocytes of naïve and memory phenotype were detected at day +60. Remarkably, we observed a very early reconstitution of antibody-secreting cells (ASC) at day +14. These ASC carried the HLA-haplotype of the donor and secreted the isotypes IgM and IgA more prevalent than IgG. They correlated with a population of CD19− CD27− CD38low/+ CD138− cells. Of note, reconstitution of this ASC occurred without detectable circulating T cells and before increase of BAFF or other B cell stimulating factors. In summary, we describe a rapid reconstitution of peripheral blood ASC after CD3 and CD19 depleted haploidentical stem cell transplantation, far preceding detection of naïve and memory type B cells. Incidence before T cell reconstitution and spontaneous secretion of immunoglobulins allocate these early ASC to innate immunity, eventually maintaining natural antibody levels.

scholarly journals The Role of Tumor-Infiltrating B Cells in Tumor Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Fei Guo ◽  
Jiu Wei Cui
Keyword(s):  
T Cells ◽  
B Cells ◽  
Tumor Immunity ◽  
Therapeutic Target ◽  
Tumor Biomarker ◽  
Potential Therapeutic Target ◽  
Tumor Inhibition ◽  
Tumor Tissues ◽  
The Relationship

Earlier studies on elucidating the role of lymphocytes in tumor immunity predominantly focused on T cells. However, the role of B cells in tumor immunity has increasingly received better attention in recent studies. The B cells that infiltrate tumor tissues are called tumor-infiltrating B cells (TIBs). It is found that TIBs play a multifaceted dual role in regulating tumor immunity rather than just tumor inhibition or promotion. In this article, latest research advances focusing on the relationship between TIBs and tumor complexity are reviewed, and light is shed on some novel ideas for exploiting TIBs as a possible tumor biomarker and potential therapeutic target against tumors.

scholarly journals TRAIL suppresses gut inflammation and inhibits colitogeic T-cell activation in experimental colitis via an apoptosis-independent pathway

2019 ◽  
Vol 12 (4) ◽  
pp. 980-989 ◽  
Author(s):  
I. T. Chyuan ◽  
H. F. Tsai ◽  
C. S. Wu ◽  
P. N. Hsu
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Bowel Disease ◽  
Cell Activation ◽  
Gut Inflammation ◽  
Inflammatory Bowel ◽  
Colitis Model

AbstractTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell apoptosis by transducing apoptosis signals. Recently, accumulating evidence demonstrated that TRAIL regulates autoimmune inflammation and immune cell homeostasis in several autoimmune animal models, suggesting a novel immunoregulatory role of TRAIL in autoimmune diseases. However, the impact of TRAIL in inflammatory bowel disease is yet undefined. This study is to address the therapeutic effects and immunoregulatory role of TRAIL in autoimmune gut inflammation. We demonstrated herein that TRAIL significantly suppressed gut inflammation and reduced the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis model. Suppression of gut inflammation was not due to induction of apoptosis in colonic T cells, dendritic cells, or epithelium cells by TRAIL. In contrast, TRAIL directly inhibited activation of colitogenic T cells and development of gut inflammation in an adoptive transfer-induced colitis model. The anti-inflammatory effects of TRAIL on colitis were abolished when T cells from TRAIL receptor (TRAIL-R) knockout mice were adoptively transferred, suggesting that TRAIL regulates autoreactive colitogenic T-cell activation in the development of gut inflammation. Our results demonstrate that TRAIL effectively inhibited colonic T-cell activation and suppressed autoimmune colitis, suggesting a potential therapeutic application of TRAIL in human inflammatory bowel disease.

scholarly journals THE ROLE OF ADIPOCYTOKINES IN COLON CANCER AND ADENOMAS / ULOGA ADIPOCITOKINA U KANCERU I ADENOMIMA DEBELOG CREVA

2013 ◽  
Vol 33 (2) ◽  
pp. 135-142 ◽  
Author(s):  
Feti Tulubas ◽  
Rafet Mete ◽  
Meltem Oznur ◽  
Birol Topcu
Keyword(s):  
Colon Cancer ◽  
Pearson Correlation ◽  
Continuous Variables ◽  
Colon Adenoma ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
And Control ◽  
The Relationship ◽  
Insulin Insensitivity

Summary Metabolic changes resulting from obesity, insulin insensitivity, and imbalances in hormones such as adiponectin, leptin, resistin, apelin and visfatin, which are derived from white adipose tissue-derived hormone, are directly linked to both colon cancer (CC) and inflammatory bowel diseases increasing tissue-derived risk. We conducted this study to evaluate the relationship between the circulating concentrations of adiponectin, leptin, resistin, apelin and visfatin and colon adenoma and CC. Our study included 90 participants aged >18 years who were divided into three groups: colon cancer, adenoma and control. The serum concentrations of the investigated adipohormones were measured with ELISA in 30 patients with colon adenoma, 30 with CC and 30 controls with no colon pathology. Demographic, anthropometric, metabolic and hormonal parameters were also recorded. The group means were compared by using one-way analysis of variance (ANOVA). Dual comparisons between groups were analyzed with the Tukey test. Pearson correlation coefficient was used to determine the relation between continuous variables. Adiponectin and leptin levels in patients with adenomas (p<0.000; p<0.000, respectively) and CC (p<0.000; p<0.000, respectively) were lower than in controls. Apelin level in patients with CC (p<0.000; p<0.000, respectively) was lower than in patients with adenomas and in controls. Resistin and visfatin levels in patients with CC (p<0.000; p<0.000, respectively) were higher than in patients with adenomas and in controls.

scholarly journals Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function

2018 ◽  
Vol 115 (41) ◽  
pp. E9630-E9639 ◽  
Author(s):  
Virginia Andreani ◽  
Senthilkumar Ramamoorthy ◽  
Abhinav Pandey ◽  
Ekaterina Lupar ◽  
Stephen L. Nutt ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Plasma Cell ◽  
Target Genes ◽  
Β1 Integrin ◽  
Plasma Cell Differentiation ◽  
And Migration ◽  
And Function ◽  
Antibody Secreting Cells

Plasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 cochaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells. By analyzing Mzb1−/−Prdm1+/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of antibody-secreting cells in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1−/− plasmablasts show a reduced activation of β1-integrin, which contributes to the impaired plasmablast differentiation and migration of antibody-secreting cells to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation.

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