Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus

Gut ◽  
2020 ◽  
Vol 69 (12) ◽  
pp. 2203-2213 ◽  
Author(s):  
Anton Lutckii ◽  
Benedikt Strunz ◽  
Anton Zhirkov ◽  
Olga Filipovich ◽  
Elena Rukoiatkina ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
B Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Cell Maturation ◽  
Innate Immune Cells ◽  
B Cell Maturation ◽  
Exposed Uninfected

ObjectivesVertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates.DesignTo address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age.ResultsAs expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines.ConclusionOur data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.

scholarly journals Characteristic pancreatic and splenic immune cell infiltration patterns in mouse acute pancreatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Baibing Yang ◽  
Joy M. Davis ◽  
Thomas H. Gomez ◽  
Mamoun Younes ◽  
Xiurong Zhao ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Pancreatitis ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Cell Infiltration ◽  
Computerized Analysis ◽  
Dimensional Flow

Abstract Background A systemic evaluation of immune cell infiltration patterns in experimental acute pancreatitis (AP) is lacking. Using multi-dimensional flow cytometry, this study profiled infiltrating immune cell types in multiple AP mouse models. Methods Three AP models were generated in C57BL/6 mice via cerulein (CAE) injection, alcohol and palmitoleic acid (EtOH + POA) injection, and alcohol diet feeding and cerulein (EtOH + CAE) injection. Primary pancreatic cells and splenocytes were prepared, and multi-dimensional flow cytometry was performed and analyzed by manual gating and computerized PhenoGraph, followed by visualization with t-distributed stochastic neighbor embedding (t-SNE). Results CAE treatment induced a time-dependent increase of major innate immune cells and a decrease of follicular B cells, and TCD4+ cells and the subtypes in the pancreas, whereas elicited a reversed pattern in the spleen. EtOH + POA treatment resulted in weaker effects than CAE treatment. EtOH feeding enhanced CAE-induced amylase secretion, but unexpectedly attenuated CAE-induced immune cell regulation. In comparison with manual gating analysis, computerized analysis demonstrated a remarkable time efficiency and reproducibility on the innate immune cells and B cells. Conclusions The reverse pattern of increased innate and decreased adaptive immune cells was consistent in the pancreas in CAE and EtOH + POA treatments. Alcohol feeding opposed the CAE effect on immune cell regulation. Together, the immune profiling approach utilized in this study provides a better understanding of overall immune responses in AP, which may facilitate the identification of intervention windows and new therapeutic strategies. Computerized analysis is superior to manual gating by dramatically reducing analysis time.

Malignant B Cells from Hairy Cell Leukemia Express an Innate Phenotype and Undergo IgD Class Switching in Response to Innate Environmental Factors, Including BAFF and APRIL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4707-4707
Author(s):  
April Chiu ◽  
Kang Chen ◽  
Bing He ◽  
Stacey Dillon ◽  
Amy Chadburn ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Immune Cells ◽  
Germinal Center ◽  
Memory B Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Class Switching

Abstract Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder characterized by massive infiltration of the spleen by malignant B cells displaying a distinctive “hairy” morphology. These hairy cells (HCs) often contain hypermutated Ig genes, suggesting an ontogenetic relationship with post-germinal center memory B cells. However, unlike memory B cells, HCs usually express CD11c and CD103, two molecules typically associated with mucosal innate immune cells. The goal of this study was to elucidate the ontogeny and growth mechanisms of HCs. We found that HCs interacted with splenic endothelial cells expressing B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), two innate B cell-stimulating factors involved in T cell-independent antibody responses, including Ig class switching. In agreement with prior studies indicating that BAFF and APRIL play an important role in B cell tumors, HCs expressed transmembrane activator and calcium modulator and cyclophylin ligand interactor (TACI), B cell maturation antigen (BCMA), and BAFF receptor (BAFF-R), three receptors that bind BAFF and APRIL. In addition, HCs expressed microbial carbohydrate and endocytic receptors usually expressed by innate immune cells, including DEC-205 (CD205), mannose receptor (CD206), langerin (CD207) and dendritic cell-specific ICAM-3-grabbing non-integrin (CD209). This phenotype was different from that of naïve, germinal center, memory and plasmacytoid B cells, but similar to that of a subset of splenic marginal zone and mucosal B cells. Like these innate B cells, HCs contained activation-induced cytidine deaminase, a DNA-editing enzyme required for class switching, and showed signs of ongoing IgM-to-IgD class switching, a mucosal Ig diversifying process typically triggered by BAFF and APRIL. Our findings suggest that HCL may emerge as a result of chronic stimulation of an innate B cell precursor through a T-cell independent pathway involving microbial carbohydrates, BAFF and APRIL.

scholarly journals Why Target Innate Immune Cells in Cancers?

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 690
Author(s):  
Mary Poupot
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells

The immune system is a smart way to fight cancer, with its precise targeting of cancer cells sparing healthy cells [...]

scholarly journals Adipocytes, Innate Immunity and Obesity: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alecia M. Blaszczak ◽  
Anahita Jalilvand ◽  
Willa A. Hsueh
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

scholarly journals Baff Binds to the Tumor Necrosis Factor Receptor–Like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population

2000 ◽  
Vol 192 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Jeffrey S. Thompson ◽  
Pascal Schneider ◽  
Susan L. Kalled ◽  
LiChun Wang ◽  
Eric A. Lefevre ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Cell Population ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Soluble Form ◽  
B Cell Maturation ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor–triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

scholarly journals Engineering advanced logic and distributed computing in human CAR immune cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jang Hwan Cho ◽  
Atsushi Okuma ◽  
Katri Sofjan ◽  
Seunghee Lee ◽  
James J. Collins ◽  
...  
Keyword(s):  
Immune Cells ◽  
Communication Channel ◽  
Immune Cell ◽  
Cell Types ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Complex Phenotypes ◽  
Car T ◽  
Different Cell Types ◽  
Multiple Immune Cell

AbstractThe immune system is a sophisticated network of different cell types performing complex biocomputation at single-cell and consortium levels. The ability to reprogram such an interconnected multicellular system holds enormous promise in treating various diseases, as exemplified by the use of chimeric antigen receptor (CAR) T cells as cancer therapy. However, most CAR designs lack computation features and cannot reprogram multiple immune cell types in a coordinated manner. Here, leveraging our split, universal, and programmable (SUPRA) CAR system, we develop an inhibitory feature, achieving a three-input logic, and demonstrate that this programmable system is functional in diverse adaptive and innate immune cells. We also create an inducible multi-cellular NIMPLY circuit, kill switch, and a synthetic intercellular communication channel. Our work highlights that a simple split CAR design can generate diverse and complex phenotypes and provide a foundation for engineering an immune cell consortium with user-defined functionalities.

scholarly journals Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery

2015 ◽  
Vol 309 (12) ◽  
pp. H2042-H2057 ◽  
Author(s):  
Sanjukta Chakraborty ◽  
Scott D. Zawieja ◽  
Wei Wang ◽  
Yang Lee ◽  
Yuan J. Wang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Contractile Activity ◽  
Macrophage Polarization ◽  
Lymphatic Vessels ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Lymphatic Function ◽  
Inflammatory Conditions ◽  
Rat Mesentery

Impairment of the lymphatic system is apparent in multiple inflammatory pathologies connected to elevated endotoxins such as LPS. However, the direct mechanisms by which LPS influences the lymphatic contractility are not well understood. We hypothesized that a dynamic modulation of innate immune cell populations in mesentery under inflammatory conditions perturbs tissue cytokine/chemokine homeostasis and subsequently influences lymphatic function. We used rats that were intraperitoneally injected with LPS (10 mg/kg) to determine the changes in the profiles of innate immune cells in the mesentery and in the stretch-mediated contractile responses of isolated lymphatic preparations. Results demonstrated a reduction in the phasic contractile activity of mesenteric lymphatic vessels from LPS-injected rats and a severe impairment of lymphatic pump function and flow. There was a significant reduction in the number of neutrophils and an increase in monocytes/macrophages present on the lymphatic vessels and in the clear mesentery of the LPS group. This population of monocytes and macrophages established a robust M2 phenotype, with the majority showing high expression of CD163 and CD206. Several cytokines and chemoattractants for neutrophils and macrophages were significantly changed in the mesentery of LPS-injected rats. Treatment of lymphatic muscle cells (LMCs) with LPS showed significant changes in the expression of adhesion molecules, VCAM1, ICAM1, CXCR2, and galectin-9. LPS-TLR4-mediated regulation of pAKT, pERK pI-κB, and pMLC20 in LMCs promoted both contractile and inflammatory pathways. Thus, our data provide the first evidence connecting the dynamic changes in innate immune cells on or near the lymphatics and complex cytokine milieu during inflammation with lymphatic dysfunction.

Dμ expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2−/− mice even if combined with Bcl-2

2006 ◽  
Vol 43 (9) ◽  
pp. 1316-1324 ◽  
Author(s):  
Ingela Wikström ◽  
Ingela Bergqvist ◽  
Dan Holmberg ◽  
Johan Forssell
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Maturation ◽  
B Cell Maturation

scholarly journals Roles of activating functions 1 and 2 of estrogen receptor α in lymphopoiesis

2018 ◽  
Vol 236 (2) ◽  
pp. 99-109 ◽  
Author(s):  
Annica Andersson ◽  
Anna E Törnqvist ◽  
Sofia Moverare-Skrtic ◽  
Angelina I Bernardi ◽  
Helen H Farman ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
Estrogen Receptors ◽  
B Cell ◽  
Sex Steroids ◽  
Cellular Response ◽  
Immune Cell ◽  
Cell Development ◽  
B Lymphopoiesis ◽  
The Impact

Apart from the role of sex steroids in reproduction, sex steroids are also important regulators of the immune system. 17β-estradiol (E2) represses T and B cell development, but augments B cell function, possibly explaining the different nature of immune responses in men and women. Both E2 and selective estrogen receptors modulators (SERM) act via estrogen receptors (ER). Activating functions (AF)-1 and 2 of the ER bind to coregulators and thus influence target gene transcription and subsequent cellular response to ER activation. The importance of ERαAF-1 and AF-2 in the immunomodulatory effects of E2/SERM has previously not been reported. Thus, detailed studies of T and B lymphopoiesis were performed in ovariectomized E2-, lasofoxifene- or raloxifene-treated mice lacking either AF-1 or AF-2 domains of ERα, and their wild-type littermate controls. Immune cell phenotypes were analyzed with flow cytometry. All E2 and SERM-mediated inhibitory effects on thymus cellularity and thymic T cell development were clearly dependent on both ERαAFs. Interestingly, divergent roles of ERαAF-1 and ERαAF-2 in E2 and SERM-mediated modulation of bone marrow B lymphopoiesis were found. In contrast to E2, effects of lasofoxifene on early B cells did not require functional ERαAF-2, while ERαAF-1 was indispensable. Raloxifene reduced early B cells partly independent of both ERαAF-1 and ERαAF-2. Results from this study increase the understanding of the impact of ER modulation on the immune system, which can be useful in the clarification of the molecular actions of SERMs and in the development of new SERM.

scholarly journals E3 Ligase UBR5 HECT domain mutations in lymphoma control maturation of B cells via alternative splicing

2019 ◽  
Author(s):  
Samantha A. Swenson ◽  
Tyler J. Gilbreath ◽  
Heather Vahle ◽  
R. Willow Hynes-Smith ◽  
Jared H. Graham ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Development ◽  
Cell Maturation ◽  
Hect Domain ◽  
B Cell Maturation ◽  
Mantle Cell

ABSTRACTCoordination of a number of molecular mechanisms including transcription, alternative splicing, and class switch recombination are required to facilitate development, activation, and survival of B cells. Disruption of these pathways can result in malignant transformation. Recently, next generation sequencing has identified a number of novel mutations in mantle cell lymphoma (MCL) patients including the ubiquitin E3 ligase UBR5. Approximately 18% of MCL patients were found to have mutations in UBR5 with the majority of mutations within the HECT domain of the protein which can accept and transfer ubiquitin molecules to the substrate. Determining if UBR5 controls the maturation of B cells is important to fully understand malignant transformation to MCL. To elucidate the role of UBR5 in B cell maturation and activation we generated a conditional mutant disrupting UBR5’s C-terminal HECT domain. Loss of the UBR5 HECT domain leads to a block in maturation of B cells in the spleen and up-regulation of proteins associated with mRNA splicing via the spliceosome. Our studies reveal a novel role of UBR5 in B cell maturation by regulating alternative splicing of key transcripts during B cell development and suggests UBR5 mutations may promote mantle cell lymphoma initiation.KEY POINTSUtilizing a novel mouse model mimicking MCL patient mutations, the loss of UBR5’s HECT domain causes alterations in B cell development.UBR5 mutations lead to stabilization of UBR5 and aberrant splicing.

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