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cellular & Molecular Immunology 2015年第1期12卷 31-39页

作者： Xiao-Mei Deng Shang-Xue Yan Wei Wei Institute of Clinical Pharmacology of Anhui Medical University Key Laboratory of Anti-inflammatory and Immune Medicine Ministry of Education HefeiChina

plasma cells, which secrete auto-antibodies, are considered to be the arch-criminal of autoimmune diseases such as systemic lupus erythematosus, but there are many cytokines involved in inducing the differentiation of B-cell subsets into plasma cells. Here, we emphasize IL-21, which has emerged as the most potent inducer of plasma cell differentiation. In this review, we focused on the promoting effects of IL-21 on plasma cell differentiation and discuss how these effects contribute to B cell-mediated autoimmune disease.

关键词： Bcl-6 Blimp-1 IL-21 plasma cell systemic lupus erythematosus

Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRLIIpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation

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cellular & Molecular Immunology 2016年第3期13卷 379-390页

作者： Yanwei Wu Shijun He Bingxin Bai Luyao Zhang Lu Xue Zemin Lin Xiaoqian Yang Fenghua Zhu Peilan He Wei Tang Jianping Zuo Laboratory of Immunopharmacology State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China Laboratory of Immunology and Virology Shanghai University of Traditional Chinese Medicine Shanghai China

We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.

关键词： B cell plasma cell SM934 systemic lupus erythematosus Toll-like receptor

B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3

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cellular & Molecular Immunology 2023年第11期20卷 1313-1327页

作者： Guojun Qian Wenxia Jiang Donglin Sun Zhun Sun Anning Chen Hongwei Fang Jingyao Wang Yongzhong Liu Zhinan Yin Haiming Wei Hao Fang Xiaoren Zhan Affiliated Cancer Hospital/Institute and GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and DiseasesState Key Laboratory of Respiratory Disease511436GuangzhouChina Shanghai Institute of Nutrition and Health Chinese Academy of Sciences200031ShanghaiChina Department of Anesthesiology Zhongshan HospitalFudan University200032ShanghaiChina Shanghai Cancer Institute Renji HospitalShanghai Jiao Tong University School of Medicine200032ShanghaiChina Zhuhai People’s Hospital Biomedical Translational Research InstituteJinan University510632GuangzhouChina Institute of Immunology University of Science and Technology of China230000HefeiChina Department of Anesthesiology Minhang HospitalFudan University201100ShanghaiChina Key Laboratory of Anesthesiology(Shanghai Jiao Tong University) Ministry of Education200001ShanghaiChina

Aeroallergen sensitization,mainly mediated by lung epithelium and dendritic cells(DCs),is integral to allergic asthma pathogenesis and progression.IL-10 has a dual role in immune responses,as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation.Here,we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma.Specifically,Bcl-3^(−/−)mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites(HDMs).IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial cells.Blockade of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma development.IL-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3–Blimp-1–Bcl-6 regulation.Mice lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization,thereby demonstrating resistance to HDM-induced asthma.Moreover,responses to HDM stimulation in Bcl-3^(−/−)mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3^(+/+)mice.The results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 production.Thus,targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma.

关键词： Bcl-3 plasma cell IL-10 Allergic sensitization Airway inflammation Asthma

Germinal center-dependent and-independent immune responses of tumor-infiltrating B cells in human cancers

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cellular & Molecular Immunology 2023年第9期20卷 1040-1050页

作者： Eve Playoust Romain Remark Eric Vivier Pierre Milpied Marseille Université CNRSINSERMCentre d’Immunologie de Marseille-LuminyMarseilleFrance Innate Pharma MarseilleFrance

B cells play essential roles in immunity,mainly through the production of high affinity plasma cells(PCs)and memory B(Bmem)cells.The affinity maturation and differentiation of B cells rely on the integration of B-cell receptor(BCR)intrinsic and extrinsic signals provided by antigen binding and the microenvironment,respectively.In recent years,tumor infiltrating B(TIL-B)cells and PCs(TIL-PCs)have been revealed as important players in antitumor responses in human cancers,but their interplay and dynamics remain largely unknown.In lymphoid organs,B-cell responses involve both germinal center(GC)-dependent and GC-independent pathways for Bmem cell and PC production.Affinity maturation of BCR repertoires occurs in GC reactions with specific spatiotemporal dynamics of signal integration by B cells.In general,the reactivation of high-affinity Bmem cells by antigens triggers GC-independent production of large numbers of PC without BCR rediversification.Understanding B-cell dynamics in immune responses requires the integration of multiple tools and readouts such as single-cell phenotyping and RNA-seq,in situ analyses,BCR repertoire analysis,BCR specificity and affinity assays,and functional tests.Here,we review how those tools have recently been applied to study TIL-B cells and TIL-PC in different types of solid tumors.We assessed the published evidence for different models of TIL-B-cell dynamics involving GC-dependent or GC-independent local responses and the resulting production of antigen-specific PCs.Altogether,we highlight the need for more integrative B-cell immunology studies to rationally investigate TIL-B cells as a leverage for antitumor therapies.

关键词： antibody tertiary lymphoid structure plasma cell germinal center cancer

Supplying the trip to antibody production-nutrients,signaling,and the programming of cellular metabolism in the mature B lineage

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cellular & Molecular Immunology 2022年第3期19卷 352-369页

作者： Mark R.Boothby Shawna K.Brookens Ariel L.Raybuck Sung Hoon Cho Department of Pathology Microbiology&ImmunologyMolecular Pathogenesis DivisionVanderbilt University Medical CenterNashvilleTN37232USA Department of Medicine Rheumatology&Immunology DivisionVanderbilt University Medical CenterNashvilleTN37232USA Cancer Biology Program Vanderbilt UniversityNashvilleTN37232USA Vanderbilt Institute of Infection Inflammationand ImmunologyNashvilleTN37232USA

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody(Ab)secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against infection.With this backdrop,it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise,persist,and meet the challenge of secreting vast amounts of these glycoproteins.Whereas plasmablasts and plasma cells(PCs)are the primary sources of secreted Abs,the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential fates.At each step,cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for nutrients.Nutrients in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription,translation,and metabolism.This review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion.Salient findings of this group and others,sometimes exhibiting differences,will be summarized with regard to the journey to a distinctive metabolic program in PCs.

关键词： B lymphocyte plasma cell Intermediary metabolism Glucose Glutamine Fatty acid Signal transduction

Role of proteasome inhibition in sensitized transplant candidates

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Chinese Medical Journal 2011年第5期124卷 771-774页

作者： Matthew J. Everly Jason J. Everly Paul I. Terasaki One Lambda Inc Research 2 Division Los Angeles CA 90064 USA

Objective To review this efficacy and safety of bortezomib, a proteasome inhibitor, in the setting of the sensitized transplant candidate. Data sources The data used in this review were from articles published （PubMed） between 2000 to 2010. Additionally abstracts from medical meetings related to transplant were also used. Study selection Articles were selected if they were trial results or case studies for the use of bortezomib in the sensitized patient population.Results The early data using bortezomib as a part of desensitization regimens has shown success. Although one cycle （4 doses） of bortezomib seems to have affect on many patients, it also seems likely that to provide complete desensitization multiple cycles will be required. Regarding safety, bortezomib has been shown to have minimal side effects. The most common side effects reported are those of thrombocytopenia and anemia. These side effects are dose related and self limiting upon discontinuation of the treatment.Conclusions Bortezomib with plasmapheresis is a promising new alternative to desensitization protocols that use either high dose intravenous immune globulin （IVIG） or low dose IVIG and plasmapheresis. The efficacy on antibody reduction looks to be batter that that of the IVIG based regimens without significant addition toxicity. The results of ongoing prospective trials are positive and their complete results are greatly anticipated.

关键词： proteasome inhibition bortezomib desensitization plasma cell alloantibodies human leukocyte antigen transplantation

Construction of Larger Area Density-Uniform plasma with Collisional Inductively Coupled plasma cells

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plasma Science and Technology 2007年第3期9卷 265-268页

作者：欧阳亮刘万东白小燕陈志鹏王慧慧李弘罗辰吉亮亮胡北 CAS Key Laboratory of Basic plasma Physics Department of Modern PhysicsUniversity of Science and Technology of ChinaHefei 230026China

The plasma density and electron temperature of a multi-source plasma system composed of several collisional inductively coupled plasma （ICP） cells were measured by a doubleprobe. The discharges of the ICP cells were shown to be independent of each other. Furthermore, the total plasma density at simultaneous multi-cell discharge was observed to be approximately equal to the summation of the plasma density when the cells discharge separately. Based on the linear summation phenomenon, it was shown that a larger area plasma with a uniform density and temperature profile could be constructed with multi-collisional ICP cells.

关键词： inductively coupled plasma collisional multi-source plasma cell

Complete resection of a huge hypervascular inflammatory myofibroblastic tumor in right hemithorax after embolization

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World Journal of Pediatrics 2016年第4期12卷 498-500页

作者： Kyu-Nam Kim Dong-Won Kim Department of Anesthesiology and Pain Medicine Hanyang University HospitalRepublic of Korea

Background:Inflammatory myofibroblastic tumor(IMT)is a rare and mostly benign tumor that has the possibility of malignant change.Methods:Radiological findings revealed a huge mass that filled most of the right hemithorax of a 17-month-old female infant.Tumor extirpation was stopped due to massive bleeding and limited exposure of the tumor.Embolization was conducted to obstruct the arteries feeding the mass.Complete resection was performed.Results:Histopathologic examination led to the diagnosis of IMT.Postoperative recovery was uneventful.Conclusion:Hypervascularity of IMT should be considered.Preoperative embolization can be effective to reduce intraoperative blood loss and facilitate the surgical procedure.

关键词： embolization granuloma mediastinal neoplasms plasma cell

Unicentric Castleman's disease associated with end stage renal disease caused by amyloidosis

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World Journal of Clinical Cases 2017年第3期5卷 119-123页

作者： Eray Eroglu Ismail Kocyigit Aydin Unal Murat Hayri Sipahioglu Hulya Akgun Leylagul Kaynar Bulent Tokgoz Oktay Oymak Division of Ne-phrology Department of Internal MedicineErciyes University School of Medicine Department of Pathology Erciyes University School of Medicine Division of Hematology Department of Internal MedicineErciyes University School of Medicine

Castleman's disease(CD), also known as angiofolicular lymph node hyperplasia, is a rare heterogenous group of lymphoproliferative disorders. Histologically, it can be classified as hyaline vascular type, plasma cell type, or mixed type. Clinically two different subtypes of the CD are present: Unicentric and multicentric. Unicentric CD is generally asymptomatic and associated with hyaline vascular type, and its diagnoses depend on the localized lymphadenopathy on examination or imaging studies. However, multicentric CD presents with generalized lymphadenopathy and systemic symptoms including malaise, fever, night sweats, weight loss, and it is associated with the plasma cell type and mix type. Herein, we report a patient with unicentric CD of the plasma cell type without systemic symptoms, who developed end stage renal failure caused by amyloidosis 6 years after onset of CD.

关键词： Castleman’s disease Amyloidosis plasma cell Inflammation End stage renal disease

Multiple Myeloma in a Patient with Rectal Cancer

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International Journal of Clinical Medicine 2022年第11期13卷 489-493页

作者： Huimin Fan Caihua Tao Department of Laboratory Medicine Zhenjiang First People’s Hospital Zhenjiang China

Multiple myeloma is characterized by the accumulation of clonal, malignant plasma cells in the bone marrow. Multiple lytic skeletal lesions in some tumor patients with multiple myeloma are easily considered as bone metastases secondary to tumors, resulting in a missed diagnosis of multiple myeloma. Herein, we report a rare case, in which rectal cancer with multiple myeloma was initially misdiagnosed with bone metastases secondary to rectal cancer, due to the symptoms of multiple lytic sketetal lesions, and ignoring the abnormal plasma cells in the peripheral circulating blood smear. The patient was finally diagnosed with coexistence of rectal cancer and multiple myeloma. The case focuses on the importance of the peripheral circulating blood smear detection.

关键词： Multiple Myeloma Multiple Lytic Skeletal Lesions plasma cell