A Role for MHC Class II Antigen Processing in B Cell Development

For mature B cells, the encounter with foreign antigen results in the selective expansion of the cells and their differentiation into antibody secreting cells or memory B cells. The response of mature B cells to antigen requires not only antigen binding to and signaling through the B cell antigen receptor (BCR) but also the processing and presentation of the BCR bound antigen to helper T cells. Thus, in mature B cells, the ability to process and present antigen to helper T cells plays a critical role in determining the outcome of antigen encounter. In immature B cells, the binding of antigen results in negative selection of the B cell, inducing apoptosis, anergy or receptor editing. Negative selection of immature B cells requires antigen induced signaling through the BCR, analogous to the signaling function of the BCR in mature B cells. However, the role of class II antigen processing and presentation in immature B cells is less well understood. Current evidence indicates that the ability to process and present antigen bound to the BCR is a late acquisition of developing B cells, suggesting that during negative selection B cells may not present BCR bound antigen and interact with helper T cells However, the expression of class II molecules is an early acquisition of B cells and recent evidence indicates that the expression of class II molecules early in development is required for the generation of long lived mature B cells. Here we review our current understanding of the processing and presentation of antigen by mature B cells and the role for antigen processing and class II expression during B cell development.     

Multitasking of Ig-α and Ig-β to Regulate B Cell Antigen Receptor Function

Since their discovery as signaling subunits of the B cell antigen receptor (BCR), Ig-α and Ig-β are discussed to serve either a redundant or distinct function for B cell development, maintenance, and activation. Dependent upon the experimental system that has been used to address this issue, evidence could be provided to support both possibilities. Only recently has it become clear that Ig-α and Ig-β possess a unique signaling identity but that both together are required to orchestrate proper B cell function in vivo. Here we discuss some of the underlying mechanisms that may involve direct coupling to discrete subsets of BCR effector proteins, such as protein tyrosine kinases or the intracellular adaptor SLP-65/BLNK.     

Antigen-Antibody Complex as Therapeutic Vaccine for Viral Hepatitis B

In a previous study, hepatitis B surface antigen (HBsAg) complexed to human anti-HBs immunoglobulins (HBIG) in excess of HBsAg was used as therapeutic vaccine to treat chronic hepatitis B patients and promising results were obtained. To study the mechanisms of this approach, mice were immunized with HBsAg or IC (immunogenic complex, i.e. HBsAg complexed with mouse polyclonal anti-HBs). Studies indicate that IC induced enhanced immune responses by increasing uptake of HBsAg through Fc receptors on antigen presenting cells and modulated HBsAg processing and presentation. This modulation led to stimulation of T cell responses, and increased production of IL-2 and IFN-γ. Assay for antibody subclasses showed that higher ratio of IgG 2a was observed in the IC immunized group, which correlated with the production of lymphokine pattern. When alum was used as the adjuvant, though antibody response was enhanced, production of cytokines decreased. When DNA from a recombinant plasmid was added to IC as an adjuvant, the liter of anti-HBs was significantly higher than those in mice immunized only with the DNA or the IC. Since DNA immunization can induce both cellular and humoral immune responses, combined immunization using IC and DNA might serve as another type of therapeutic vaccine for viral hepatitis B.     

Sample pooling: burden or solution?

BackgroundPool-testing strategies combine samples from multiple people and test them as a group. A pool-testing approach may shorten the screening time and increase the test rate during times of limited test availability and inadequate reporting speed. Pool testing has been effectively used for a wide variety of infectious disease screening settings. Historically, it originated from serological testing in syphilis. During the current coronavirus disease 2019 (COVID-19) pandemic, pool testing is considered across the globe to inform opening strategies and to monitor infection rates after the implementation of interventions.AimsThis narrative review aims to provide a comprehensive overview of the global efforts to implement pool testing, specifically for COVID-19 screening.SourcesData were retrieved from a detailed search for peer-reviewed articles and preprint reports using Medline/PubMed, medRxiv, Web of Science, and Google up to 21st March 2021, using search terms “pool testing”, “viral”, “serum”, “SARS-CoV-2” and “COVID-19”.ContentThis review summarizes the history and theory of pool testing. We identified numerous peer-reviewed articles that describe specific details and practical implementation of pool testing. Successful examples as well as limitations of pool testing, in general and specifically related to the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies, are reviewed. While promising, significant operational, pre-analytical, logistical, and economic challenges need to be overcome to advance pool testing.ImplicationsThe theory of pool testing is well understood and numerous successful examples from the past are available. Operationalization of pool testing requires sophisticated processes that can be adapted to the local medical circumstances. Special attention needs to be paid to sample collection, sample pooling, and strategies to avoid re-sampling.     

泛素编辑蛋白A20对呼吸机相关性肺炎患者单核细胞活性的影响

目的观察并分析泛素编辑蛋白A20对呼吸机相关性肺炎(ventilator associated pneumonia,VAP)患者单核细胞活性的影响。方法入选2019年2月至9月在郑州大学第一附属医院诊断为VAP的患者24例(VAP组)和健康对照12例(对照组)。分离VAP组外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)、感染部位和非感染部位的支气管肺泡灌洗液(bronchial alveolar lavage fluid,BALF)及对照组PBMCs,检测CD14⁺单核细胞中A20水平。纯化VAP患者CD14⁺单核细胞和CD4⁺T细胞,使用A20 siRNA转染CD14⁺单核细胞。转染的CD14⁺单核细胞与自体CD4⁺T细胞直接/间接接触共培养,检测CD4⁺T细胞分泌干扰素-γ(interferon-γ,IFN-γ)和白细胞介素-17(interleukin-17,IL-17)水平。转染的CD14⁺单核与NCI-H889细胞直接/间接共培养,检测细胞毒性、分泌细胞因子、颗粒酶B水平及肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis inducing ligand,TRAIL)、FasL配体(Fas ligand,FasL)水平。组间比较采用成组t检验或SNK-q检验。结果VAP组外周血CD14⁺A20⁺细胞比例高于对照组[(62.61±15.33)%vs.(47.13±11.82),P<0.05],A20平均荧光强度(mean fluorescence intensity,MFI)亦高于对照组[(227.9±64.18)vs.(178.2±58.62),P<0.05]。VAP组感染部位BALF中的CD14⁺A20⁺细胞比例高于未感染部位[(66.14±19.62)%vs.(52.52±13.71)%,P<0.05],A20 MFI亦高于未感染部位[(268.0±72.56)vs.(197.4±60.01),P<0.05]。A20 siRNA转染的VAP患者外周血和BALF中的CD14⁺单核细胞与自体CD4⁺T细胞直接接触共培养后,CD4⁺T细胞分泌IFN-γ和IL-17的细胞比例均高于未转染和siRNA转染(P<0.05),但间接接触共培养中,CD4⁺IFN-γ⁺和CD4⁺IL-17⁺细胞比例在未转染、对照siRNA转染和A20 siRNA转染中的差异无统计学意义(P>0.05)。A20 siRNA转染的VAP患者外周血和BALF中的CD14⁺单核细胞与NCI-H889细胞直接/间接接触共培养后,靶细胞死亡比例均高于未转染和siRNA转染(P<0.05),肿瘤坏死因子-α、IL-6、颗粒酶B水平及TRAIL MFI亦高于未转染和siRNA转染(P<0.05),但靶细胞死亡比例在直接接触和间接接触共培养之间的差异无统计学意义(P>0.05)。结论VAP患者单核细胞中A20水平升高,可能发挥抑制单核细胞活性的作用.     

猪囊尾蚴病免疫和诊断抗原的分子生物学研究进展

猪囊尾蚴病是一种危害严重的人兽共患寄生虫病。猪囊尾蚴特异性和保护性抗原的研究是猪带绦虫病、猪囊尾蚴病免疫和诊断的基础。天然抗原来源有限,限制了其应用,而重组抗原的应用可解决质量控制和抗原来源的问题。该文就近年来猪囊尾蚴病免疫和诊断抗原的分子生物学研究进展进行了综述。