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B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma

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Cellular & Molecular Immunology 2015年第2期12卷 202-212页

作者： Sumit Ghosh Scott A Hoselton Scott V Asbach breanne N Steffan Steve b Wanjara Glenn P Dorsam Jane M Schuh Department of Veterinary and Microbiological Sciences North Dakota State University Fargo ND USA

Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. JH-/- mice lack the JHgene for the heavy chain component of antibodies, which is critical for b-cell function and survival. These animals have facilitated the elucidation of the role of b iymphocytes in a number of immune responses; however, JH-/- mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type bALb/c and JH-/- mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of JH-/- mice relative to the bALb/c controls. by contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the JH-/- animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exDosure in the pulmonary compartment.

关键词： Aspergillus fumigatus B lymphocytes inflammation

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IRF4 and IRF8： governing the virtues of B lymphocytes

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Frontiers in biology 2014年第4期9卷 269-282页

作者： Vipul SHUKLA Runqing LU Department of Genetics Cell Biology & Anatomy University of Nebraska Medical Center Omaha NE 68198 USA

Interferon regulatory factor 4 （IRF4） and IRF8 are critical regulators of immune system development and function. In B lymphocytes, IRF4 and IRF8 have been shown to control important events during their development and maturation including pre-b cell differentiation, induction of b cell tolerance pathways, marginal zone b cell development, germinal center reaction and plasma cell differentiation. Mechanistically, IRF4 and IRF8 are found to function redundantly to control certain stages of b cell development, but in other stages, they function nonredundantly to play distinct roles in b cell biology. In line with their essential roles in b cell development, deregulated expressions of IRF4 and IRF8 have been associated to the pathogenesis of several b cell malignancies and diseases. Recent studies have elucidated diverse transcriptional networks regulated by IRF4 and IRF8 at distinct b cell developmental stages and related malignancies. In this review we will discuss the recent advances for the roles of IRF4 and IRF8 during b cell development and associated diseases.

关键词： IRF4 IRF8 B lymphocytes transcriptional regulation leukemia and lymphoma b cell development

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Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

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Cell Research 2001年第1期11卷 44-54页

作者： ZAMORANO JOSE,Unidad de Investigacion, Hospital San Pedro de Alcantara, Avda Millan Astray, 10003 Caceres ANN E KELLY, JONATHAN AUSTRIAN, HELEN Y WANG, ACHSAH D KEEGAN (Department of Immunology, Jerome Holland Labs, American Red Cross, Rockville, MD, USA 1Department of Immunology Jerome Holland Labs American Red Cross Rockville MD USA 1Department of Immunology Jerome Holland Labs American Red Cross Rockville MD USA 1Department of Immunology Jerome Holland Labs American Red Cross Rockville MD USA 1Department of Immunology Jerome Holland Labs American Red Cross Rockville MD USA 1Department of Immunology Jerome Holland Labs American Red Cross Rockville MD USA

IL-4 is an important b cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3’ kinase in both resting and activated cells. by contrast, association of phosphorylated IRS2 with GRb2 was not detected in resting b cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRb2 in b cell blasts. The pattern of IL-4- induced recruitment of p85 and GRb2 to IRS2 observed in b cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEKI inhibitor suppressed the IL-4-induced proliferative response of LPS-activated b cell blasts. These results demonstrate that costimulation of splenic b cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

关键词： B lymphocytes IL-4 survival proliferation.

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A preliminary study of the immunomodulatory function of human amniotic fluid stem cells on B lymphocytes

A preliminary study of the immunomodulatory function of huma...

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第十二届全国免疫学学术大会

作者： Yin Zhou Varshithreddy Nagam Liang Han-si Zhang Xue-Guang Gu Yan-Zheng Xue Qun The First Affiliated Hospital of Soochow University

Objective:The aims of this study were to investigate the immunomodulatory function of human amniotic fluid stem cells(hAFSCs) on B lymphocytes and to provide a theoretical basis for the treatment of autoimmune diseases with these cells.Methods:hAFSCs were isolated and cultured by the adherent method,and then were identified by characteristic phenotypic markers.After coculture of B lymphocytes with hAFSCs,the proliferation,apoptosis,differentiation,chemotaxis,and expression of the inhibitory costimulatory molecules b7 H1,b7 H3,and b7 H4 of B lymphocytes as well as the subtypes of B lymphocytes were examined in vitro.Results:B lymphocytes were activated by the costimulatory molecules,and coculture with hAFSCs significantly decreased the expression of CD80/CD86 on activated B lymphocytes.Coculture with hAFSCs resulted in a significant decrease in Ki-67 expression as well as inhibition of b lymphocyte apoptosis.hAFSCs could inhibit the expression of b7 H4 and PD-L1 on the activated B lymphocytes.The expression of the chemokine CCR7 on both activated and nonactivated B lymphocytes was downregulated by coculture with hAFSCs.In activated B lymphocytes,coculture with hAFSCs resulted in a reduced proportion of memory b and plasma cells,resulting in reduced amounts of immunoglobulins IgM,IgA,and IgG.hAFSCs could balance the b1 to b2 cell subpopulation ratio by downregulating the proportion of b1 cells.Conclusion:hAFSCs could inhibit the proliferation,apoptosis,chemotaxis,and differentiation as well as expression of costimulatory molecules of human B lymphocytes in vitro,indicating hAFSCs as ideal seed cells with therapeutic potential for treating autoimmune diseases.

关键词： human amniotic fluid stem cells B lymphocytes immune regulation autoimmune diseases

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Activation-induced cell death in B lymphocytes

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Cell Research 2000年第3期10卷 179-192页

作者： DONJERKOVIC DUbRAVKA, DAVID W SCOTT (Department of Immunology, Holland Laboratory for the biomedical Sciences, American Red Cross, 15601 Crabbs branch Way, Rockville, MD, 20855. USA) DepartmentofImmunology AmericanRedCrossRockvilleMD20855USA.

Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of b cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the b cell receptor (bCR). bCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), bCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the b cell fate and, consequently, the immune response.

关键词： B lymphocytes activation-induced cell death b cell receptor.

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bystanders or not?Microglia and lymphocytes in aging and stroke

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Neural Regeneration Research 2023年第7期18卷 1397-1403页

作者： Justin N.Nguyen Anjali Chauhan University of Texas McGovern Medical School at Houston HoustonTXUSA Department of Neurology University of Texas McGovern Medical School at HoustonHoustonTXUSA

As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.

关键词： age B lymphocytes brain central nervous system cognition inflammation microglia middle cerebral artery occlusion neuroinflammation stroke T lymphocytes white matter injury

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berberine might block colorectal carcinogenesis by inhibiting the regulation of b-cell function by Veillonella parvula

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Chinese Medical Journal 2023年第22期136卷 2722-2731页

作者： Yun Qian Ziran Kang Licong Zhao Huimin Chen Chengbei Zhou Qinyan Gao Zheng Wang Qiang Liu Yun Cui Xiaobo Li Yingxuan Chen Tianhui Zou Jingyuan Fang Division of Gastroenterology and Hepatology Shanghai Institute of Digestive DiseaseNHC Key Laboratory of Digestive DiseasesState Key Laboratory for Oncogenes and Related GenesRenji HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Department of General Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Department of Pathology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China

background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(bbR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of bbR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the bbR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after bbR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13b(Tumor necrosis factor superfamily 13b,encoding b lymphocyte stimulator[bLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased bLyS levels,while bbR reversed this effect.Conclusion:bbR might inhibit V.parvula and further weaken the immunomodulatory effect of b cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.

关键词： Colorectal cancer berberine Gut microbiota Intestinal immune pathway B lymphocytes

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Advances in immunopathogenesis of adult immune thrombocytopenia

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Frontiers of Medicine 2013年第4期7卷 418-424页

作者： Xinguang Liu Yu Hou Jun Peng Department of Hematology Qilu HospitalShandong UniversityJinan 250012China Shandong University School of Medicine Jinan250012China

Primary immune thrombocytopenia(ITP)is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production.Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP,several abnormalities involving the cellular mechanisms of immune modulation have been identified,and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction.This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

关键词： primary immune thrombocytopenia B lymphocytes T lymphocytes antigen-presenting cells cytokines

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Possible relationship between intestinal barrier function and formation of pigment gallstones in hamsters

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Hepatobiliary & Pancreatic Diseases International 2008年第5期7卷 529-532页

作者： Fan, Ying Wu, Shuo-Dong Sun, Lei Fu, bei-bei Su, Yang China Med Univ Shengjing Hosp Dept Gen Surg Shenyang 110004 Peoples R China

bACKGROUND: The presence of bacteria in bile is an important factor in the formation of pigment gallstones. The bile of healthy people is sterile and bacteria in the biliary system come from endogenous infection from the gut. Yet, the route of bacterial translocation into the bile duct is still unclear. Theoretically, two routes exist: one is through the intestinal barrier and the other is by direct reflux from the sphincter of Oddi. This study was undertaken to explore the relationship between the effectiveness of intestinal barrier and the formation of pigment gallstones in hamsters. METHODS: Thirty-two hamsters were divided into an experimental and a control group, with 16 hamsters in each group. A low protein and high cellulose diet was given for 6 weeks to induce the formation of pigment gallstones in the experimental group (PS) and a normal diet was given to the control group (CON). Morphological changes, changes in the levels of serum endotoxin and diamine oxidase, and changes in the numbers of B lymphocytes, plasma cells and secretory immunoglobin A (sIgA) in the intestinal mucosa were assessed after 6 weeks. RESULTS: Four hamsters died during lithogenesis and body weight decreased in the PS group. Pigment gallstones were found in 11 hamsters at the end of the experiment, giving a lithogenesis rate of 91.67%. The serum endotoxin level before and after gallstone formation in the PS group was 0.2960 +/- 0.1734 U/ml and 8.2964 +/- 4.6268 U/ml, respectively (Pblood diamine oxidase level before and after gallstone formation in the PS group was 2.6333 +/- 0.8037 U/ml and 3.3642 +/- 0.9545 U/ml, respectively (Pbers of B lymphocytes, plasma cells and sIgA in the intestinal mucosa in the PS group were 71.56 +/- 2.89, 68.65 +/- 2.09 and 27.56 +/- 1.07, respectively, and were significantly decreased compared with the corresponding values in the CON group (94.25 +/- 3.69, 93.47 +/- 3.98 and 42.57 +/- 1.96, respectively, P<0.05). CONCLUSIONS: A low protein and high cellulose diet can markedl

关键词： endotoxins diamine oxidase B lymphocytes plasma cells secretory immunoglobin A

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The percentage of b lymphocyte may become a good predictor of insulin resistance in women with gestational diabetes mellitus

The percentage of B lymphocyte may become a good predictor o...

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第十二届全国免疫学学术大会

作者： Zhuang Yan He Yinyan Shanghai General Hospital

ObJECTIVES Gestational diabetes mellitus(GDM) is related to insulin resistance and the dysfunction of insulin b cells.Chronic low grade inflammation and related immune damage are referred to be involved in insulin resistance.Our study aimed to explore the correlation between immune cells and insulin resistance.Methods:The clinical and biochemical characteristics of 168 healthy pregnant women and 124 pregnant women with GDM enrolled in our study were analyzed by statistic methods.Cells in the blood of women presented with GDM were then selected by flow cytometry and the data were analyzed by RT-PCR.In that the percentage of B lymphocytes was different between healthy women and women with GDM,antibodies of B lymphocytes were then selected by flow cytometry.Pearson correlation analysis was performed to reveal the correlation between the percentage of B lymphocytes and insulin resistance.We determined a cut-off for the percentage of B lymphocytes based on insulin resistance using receiver operating characteristic(ROC) curves.Results:Compared with healthy pregnant women the level of triglyceride,cholesterol and the ratio of B lymphocytes were different in women with GDM.The percentage of B lymphocytes was positively related with insulin resistance.And the IgA antibody produced by B lymphocytes was different between healthy women and pregnant women with GDM.The ratio of 14.5%of the percentage of B lymphocytes was the reasonable cutoff to predict insulin resistance in GDM.Conclusions:The percentage of b lymphocyte was related with insulin resistance in women with GDM.It may become a good predictor of insulin resistance in GDM women.

关键词： B lymphocytes insulin resistance GDM

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