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New insights into the mechanisms regulating plasma cell survival and longevity 浆细胞存活和寿命调节机制的新见解。
IF 6.6 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.coi.2024.102442
Mélanie Khamyath , Houda Melhem , Karl Balabanian , Marion Espéli

Plasma cells correspond to the last stage of B cell differentiation and are professional antibody-secreting cells. While most persist for only few days, some may survive for weeks to years in dedicated survival niches. The determination of plasma cell survival rate seems to rely both on intrinsic and extrinsic factors. Although often opposed, the deterministic and environmental models for plasma cell longevity are certainly overlapping. Understanding the contribution and the regulation of these different factors is paramount to develop better vaccines but also to target malignant plasma cells. Here, we review recent literature highlighting new findings pertaining to plasma cell survival rate, intrinsic regulation of plasma cell persistence and function, as well as the plasma cell/niche dialogue. Moreover, the now well-recognised heterogeneity observed among plasma cells is also discussed.

浆细胞相当于 B 细胞分化的最后阶段,是专业的抗体分泌细胞。虽然大多数浆细胞只能存活数天,但也有一些浆细胞可以在专门的存活龛中存活数周至数年。决定浆细胞存活率的因素似乎既有内在因素,也有外在因素。浆细胞寿命的决定性模型和环境模型虽然经常对立,但两者肯定是重叠的。了解这些不同因素的作用和调控对于开发更好的疫苗和靶向恶性浆细胞至关重要。在此,我们回顾了最近的文献,重点介绍了有关浆细胞存活率、浆细胞持久性和功能的内在调控以及浆细胞/基因对话的新发现。此外,我们还讨论了目前公认的浆细胞间的异质性。
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引用次数: 0
The tumor-driven antibody-mediated immune response in cancer 癌症中由肿瘤驱动的抗体介导的免疫反应。
IF 6.6 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.coi.2024.102431

Immune cells in the tumor microenvironment play a crucial role in cancer prognosis and response to immunotherapy. Recent studies highlight the significance of tumor-infiltrating B cells and tertiary lymphoid structures as markers of favorable prognosis and patient-positive response to immune checkpoint blockers in some types of cancer. Although the presence of germinal center B cells and plasma cells in the tumor microenvironment has been established, determining their tumor reactivity remains challenging. The few known tumor targets range from viral proteins to self and altered self-proteins. The emergence of self-reactive antibodies in patients with cancer, involves the opposing forces of antigen-driven affinity increase and peripheral tolerance mechanisms. Here, B cell tumor antigen specificity and affinity maturation in tumor-directed immune responses in cancer are discussed.

肿瘤微环境中的免疫细胞在癌症预后和对免疫疗法的反应中起着至关重要的作用。最近的研究强调了肿瘤浸润 B 细胞和三级淋巴结构的重要性,它们是某些类型癌症预后良好和患者对免疫检查点阻断剂反应阳性的标志。虽然生殖中心 B 细胞和浆细胞在肿瘤微环境中的存在已被证实,但确定它们的肿瘤反应性仍具有挑战性。已知的少数肿瘤靶点包括病毒蛋白、自身蛋白和改变的自身蛋白。癌症患者体内自身反应性抗体的出现涉及抗原驱动的亲和力增强和外周耐受机制的对立力量。在此,我们将讨论B细胞肿瘤抗原特异性和亲和力成熟在肿瘤导向的癌症免疫反应中的作用。
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引用次数: 0
Advances and challenges in investigating B-cells via single-cell transcriptomics 通过单细胞转录组学研究 B 细胞的进展与挑战。
IF 6.6 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.coi.2024.102443
Oliver P Skinner, Saba Asad, Ashraful Haque

Single-cell RNA sequencing (scRNAseq) and Variable, Diversity, Joining (VDJ) profiling have improved our understanding of B-cells. Recent scRNAseq-based approaches have led to the discovery of intermediate B-cell states, including preplasma cells and pregerminal centre B-cells, as well as unveiling protective roles for B-cells within tertiary lymphoid structures in respiratory infections and cancers. These studies have improved our understanding of transcriptional and epigenetic control of B-cell development and of atypical and memory B-cell differentiation. Advancements in temporal profiling in parallel with transcriptomic and VDJ sequencing have consolidated our understanding of the trajectory of B-cell clones over the course of infection and vaccination. Challenges remain in studying B-cell states across tissues in humans, in relating spatial location with B-cell phenotype and function, in examining antibody isotype switching events, and in unequivocal determination of clonal relationships. Nevertheless, ongoing multiomic assessments and studies of cellular interactions within tissues promise new avenues for improving humoral immunity and combatting autoimmune conditions.

单细胞 RNA 测序(scRNAseq)和变异、多样性、连接(VDJ)分析增进了我们对 B 细胞的了解。最近基于 scRNAseq 的方法发现了 B 细胞的中间状态,包括前浆细胞和前芽胞中心 B 细胞,并揭示了三级淋巴结构中的 B 细胞在呼吸道感染和癌症中的保护作用。这些研究提高了我们对 B 细胞发育的转录和表观遗传控制以及非典型和记忆性 B 细胞分化的认识。与转录组学和 VDJ 测序同时进行的时间谱分析的进步,巩固了我们对 B 细胞克隆在感染和疫苗接种过程中的轨迹的理解。在研究人体各组织中的 B 细胞状态、将空间位置与 B 细胞表型和功能联系起来、检查抗体异型转换事件以及明确确定克隆关系方面仍存在挑战。不过,正在进行的多组学评估和组织内细胞相互作用研究有望为改善体液免疫和对抗自身免疫疾病提供新的途径。
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引用次数: 0
Yin and yang of interferons: lessons from the coronavirus disease 2019 (COVID-19) pandemic 干扰素的阴与阳:2019 年冠状病毒病(COVID-19)大流行的教训
IF 7 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.1016/j.coi.2024.102423
Sara Svensson Akusjärvi , Ivan Zanoni

The host immune response against severe acute respiratory syndrome coronavirus 2 includes the induction of a group of natural antiviral cytokines called interferons (IFNs). Although originally recognized for their ability to potently counteract infections, the mechanistic functions of IFNs in patients with varying severities of coronavirus disease 2019 (COVID-19) have highlighted a more complex scenario. Cellular and molecular analyses have revealed that timing, location, and subtypes of IFNs produced during severe acute respiratory syndrome coronavirus 2 infection play a major role in determining disease progression and severity. In this review, we summarize what the COVID-19 pandemic has taught us about the protective and detrimental roles of IFNs during the inflammatory response elicited against a new respiratory virus across different ages and its longitudinal consequences in driving the development of long COVID-19.

宿主对严重急性呼吸系统综合征冠状病毒2的免疫反应包括诱导一组名为干扰素(IFNs)的天然抗病毒细胞因子。尽管干扰素最初被认为能够有效抵御感染,但其在不同严重程度的 2019 年冠状病毒疾病(COVID-19)患者体内的机理功能凸显了更为复杂的情况。细胞和分子分析表明,严重急性呼吸系统综合征冠状病毒2感染期间产生的IFNs的时间、位置和亚型在决定疾病进展和严重程度方面起着重要作用。在这篇综述中,我们总结了 COVID-19 大流行给我们带来的启示,即 IFNs 在不同年龄段针对新型呼吸道病毒引起的炎症反应中的保护性和损害性作用,及其在推动 COVID-19 长程发展中的纵向后果。
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引用次数: 0
Adaptive immune receptor germline gene variation 适应性免疫受体种系基因变异。
IF 7 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.1016/j.coi.2024.102429
Martin M Corcoran, Gunilla B Karlsson Hedestam

Recognition of antigens by T cell receptors (TCRs) and B cell receptors (BCRs) is a key step in lymphocyte activation. T and B cells mediate adaptive immune responses, which protect us against infections and provide immunological memory, and also, in some instances, drive pathogenic responses in autoimmune diseases. TCRs and BCRs are encoded within loci that are known to be genetically diverse. However, the extent and functional impact of this variation, both in humans and model animals used in immunological research, remain largely unknown. Experimental and genetic evidence has demonstrated that the complementarity determining regions 1 and 2 (HCDR1 and HCDR2), encoded by the variable (V) region of TCRs and BCRs, also often make critical contacts with the targeted antigen. Thus, knowledge about allelic variation in the genes encoding TCRs and BCRs is critically important for understanding adaptive immune responses in outbred populations and to define responder and non-responder phenotypes.

T 细胞受体(TCR)和 B 细胞受体(BCR)识别抗原是淋巴细胞活化的关键步骤。T 细胞和 B 细胞介导适应性免疫反应,保护我们免受感染并提供免疫记忆,在某些情况下还会驱动自身免疫性疾病的致病反应。TCR 和 BCR 在已知具有遗传多样性的基因座中编码。然而,这种变异在人类和免疫学研究中使用的模式动物中的程度和功能影响在很大程度上仍然未知。实验和遗传学证据表明,由 TCR 和 BCR 的可变区(V)编码的互补性决定区 1 和 2(HCDR1 和 HCDR2)也经常与目标抗原发生关键接触。因此,了解编码 TCR 和 BCR 的基因的等位基因变异对于了解外源种群的适应性免疫反应以及确定应答者和非应答者表型至关重要。
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引用次数: 0
In search of a function for human type III interferons: insights from inherited and acquired deficits 寻找人类 III 型干扰素的功能:从遗传性和获得性缺陷中获得启示
IF 7 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.1016/j.coi.2024.102427
Qian Zhang , Kai Kisand , Yi Feng , Darawan Rinchai , Emmanuelle Jouanguy , Aurélie Cobat , Jean-Laurent Casanova , Shen-Ying Zhang

The essential and redundant functions of human type I and II interferons (IFNs) have been delineated over the last three decades by studies of patients with inborn errors of immunity or their autoimmune phenocopies, but much less is known about type III IFNs. Patients with cells that do not respond to type III IFNs due to inherited IL10RB deficiency display no overt viral disease, and their inflammatory disease phenotypes can be explained by defective signaling via other interleukine10RB-dependent pathways. Moreover, patients with inherited deficiencies of interferon-stimulated gene factor 3 (ISGF-3) (STAT1, STAT2, IRF9) present viral diseases also seen in patients with inherited deficiencies of the type I IFN receptor (IFNAR1/2). Finally, patients with autoantibodies neutralizing type III IFNs have no obvious predisposition to viral disease. Current findings thus suggest that type III IFNs are largely redundant in humans. The essential functions of human type III IFNs, particularly in antiviral defenses, remain to be discovered.

在过去的三十年里,通过对先天性免疫错误患者或其自身免疫表型的研究,人类 I 型和 II 型干扰素(IFNs)的基本功能和冗余功能已经得到了明确的界定,但人们对 III 型 IFNs 的了解却少得多。因遗传性 IL10RB 缺乏而导致细胞对 III 型 IFNs 没有反应的患者不会表现出明显的病毒性疾病,他们的炎症性疾病表型可以通过其他白细胞介素-10RB 依赖性途径的信号传递缺陷来解释。此外,遗传性干扰素刺激基因因子 3(ISGF-3)(STAT1、STAT2、IRF9)缺乏症患者也会出现病毒性疾病,这在遗传性 IFN 受体(IFNAR1/2)缺乏症患者身上也能看到。最后,自身抗体中和Ⅲ型IFN的患者没有明显的病毒性疾病倾向。因此,目前的研究结果表明,III 型 IFN 在人类体内基本上是多余的。人类 III 型 IFNs 的基本功能,尤其是抗病毒防御功能,仍有待发现。
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引用次数: 0
Help me help you: emerging concepts in T follicular helper cell differentiation, identity, and function 帮我帮你:T 滤泡辅助细胞分化、特性和功能的新概念
IF 7 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.1016/j.coi.2024.102421
Sebastian A Wellford, Pamela L Schwartzberg

Effective high-affinity, long-term humoral immunity requires T cell help provided by a subset of differentiated CD4+ T cells known as T follicular helper (Tfh) cells. Classically, Tfh cells provide contact-dependent help for the generation of germinal centers (GCs) in secondary lymphoid organs (SLOs). Recent studies have expanded the conventional definition of Tfh cells, revealing new functions, new descriptions of Tfh subsets, new factors regulating Tfh differentiation, and new roles outside of SLO GCs. Together, these data suggest that one Tfh is not equivalent to another, helping redefine our understanding of Tfh cells and their biology.

有效的高亲和力长期体液免疫需要分化的 CD4+ T 细胞亚群,即 T 滤泡辅助细胞(Tfh)提供的 T 细胞帮助。传统上,Tfh 细胞为次级淋巴器官(SLO)中生殖中心(GCs)的生成提供依赖接触的帮助。最近的研究扩展了 Tfh 细胞的传统定义,揭示了新的功能、对 Tfh 亚群的新描述、调节 Tfh 分化的新因素以及在 SLO GCs 以外的新作用。这些数据共同表明,一种 Tfh 并不等同于另一种 Tfh,有助于重新定义我们对 Tfh 细胞及其生物学的认识。
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引用次数: 0
Type III interferons in innate and adaptive immunity in the respiratory tract 呼吸道先天性和适应性免疫中的 III 型干扰素。
IF 7 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.1016/j.coi.2024.102430
Artemios Piperakis, Ioanna E Galani, Evangelos Andreakos

Lambda interferons (IFNλs), also termed type III interferons (IFNs) or interleukins-28/29, have been in the shadow of type I IFNs for a long time. Their common induction mechanisms and signalling cascades with type I IFNs have made difficult the unwinding of their unique nonredundant functions. However, this is now changing with mounting evidence supporting a major role of IFNλs as a specialized antiviral defense system in the body, mediating protection at mucosal barrier surfaces while limiting immunopathology.

Here, we review the latest progress on the complex activities of IFNλs in the respiratory tract, focusing on their multiple effects in IFNλ receptor-expressing cells, the modulation of innate and adaptive immune responses in the context of infections and respiratory diseases, and their similarities and differences with type I IFNs. We also discuss their potential in therapeutic applications and the most recent developments in that direction.

λ型干扰素(IFNλs)又称 III 型干扰素(IFNs)或白细胞介素-28/29,长期以来一直处于 I 型干扰素的阴影之下。它们与 I 型干扰素具有共同的诱导机制和信号级联,这使得人们难以解读它们独特的非冗余功能。然而,随着越来越多的证据支持 IFNλs 在机体中作为专门的抗病毒防御系统发挥重要作用,在限制免疫病理的同时介导粘膜屏障表面的保护,这种情况现在正在发生变化。在此,我们回顾了 IFNλs 在呼吸道中复杂活动的最新进展,重点是它们在 IFNλ 受体表达细胞中的多重作用、在感染和呼吸道疾病中对先天性和适应性免疫反应的调节,以及它们与 I 型 IFNs 的异同。我们还讨论了它们在治疗方面的应用潜力以及这方面的最新进展。
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引用次数: 0
Regulation of host/pathogen interactions in the gastrointestinal tract by type I and III interferons I 型和 III 型干扰素对胃肠道中宿主/病原体相互作用的调节。
IF 7 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.1016/j.coi.2024.102425
Gowri Kalugotla , Vivien Marmerstein , Megan T Baldridge

Interferons (IFNs) are an integral component of the host innate immune response during viral infection. Recent advances in the study of type I and III IFNs suggest that though both types counteract viral infection, type III IFNs act predominantly at epithelial barrier sites, while type I IFNs drive systemic responses. The dynamics and specific roles of type I versus III IFNs have been studied in the context of infection by a variety of enteric pathogens, including reovirus, rotavirus, norovirus, astrovirus, and intestinal severe acute respiratory syndrome coronavirus 2, revealing shared patterns of regulatory influence. An important role for the gut microbiota, including the virome, in regulating homeostasis and priming of intestinal IFN responses has also recently emerged.

干扰素(IFNs)是病毒感染期间宿主先天免疫反应不可或缺的组成部分。对 I 型和 III 型 IFNs 研究的最新进展表明,虽然两种类型的 IFNs 都能抵御病毒感染,但 III 型 IFNs 主要作用于上皮屏障部位,而 I 型 IFNs 则驱动全身反应。在多种肠道病原体感染的背景下,对 I 型和 III 型 IFNs 的动态和特定作用进行了研究,这些病原体包括雷诺病毒、轮状病毒、诺如病毒、星状病毒和肠道严重急性呼吸综合征冠状病毒 2,揭示了共同的调控影响模式。最近还出现了肠道微生物群(包括病毒群)在调节肠道 IFN 反应的平衡和启动方面的重要作用。
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引用次数: 0
Nutritional modulation of antitumor immunity 营养调节抗肿瘤免疫力
IF 7 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-04-01 DOI: 10.1016/j.coi.2024.102422
Mingeum Jeong , Nicholas Collins

The composition and quantity of food we eat have a drastic impact on the development and function of immune responses. In this review, we highlight defined nutritional interventions shown to enhance antitumor immunity, including ketogenic, low-protein, high-fructose, and high-fiber diets, as well as dietary restriction. We propose that incorporating such nutritional interventions into immunotherapy protocols has the potential to increase therapeutic responsiveness and long-term tumor control in patients with cancer.

我们所吃食物的成分和数量对免疫反应的发展和功能有着巨大的影响。在这篇综述中,我们重点介绍了已确定的可增强抗肿瘤免疫力的营养干预措施,包括生酮饮食、低蛋白饮食、高果糖饮食和高纤维饮食以及饮食限制。我们认为,将此类营养干预措施纳入免疫疗法方案有可能提高癌症患者的治疗反应性和长期肿瘤控制率。
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引用次数: 0
期刊
Current Opinion in Immunology
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