Humoral Immunity by Anergic B cells
无能 B 细胞的体液免疫
基本信息
- 批准号:10460932
- 负责人:
- 金额:$ 51.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-07-03 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAffinityAntibodiesAntibody FormationAntibody ResponseAntigen ReceptorsAntigensAutoantibodiesAutoantigensAutoimmuneAutoimmune DiseasesAutoimmunityB-LymphocytesBone MarrowCD4 Positive T LymphocytesCellsDevelopmentDiseaseEtiologyGenesGeneticGoalsHIVHIV envelope proteinHIV-1Histone H2AHumanHumoral ImmunitiesHydralazineImmune EvasionImmune SeraImmune ToleranceImmune responseImmune systemImmunityImmunizationImmunizeImmunoglobulin Somatic HypermutationImpairmentIn VitroIndividualInfectionMemoryModelingMolecular MimicryMusNaturePathway interactionsPeripheralPharmaceutical PreparationsPhysiologicalPopulationPristaneProcessProductionProteinsSpleenStimulusTimeViralVirusWild Type MouseWorkanergyautoreactive B cellautoreactivitybasecentral toleranceclinical subtypesclinically relevantcross reactivityenv Gene Productsexperimental studyhazardhumanized mousein vivoinsightmimicrymouse modelneutralizing antibodyneutralizing monoclonal antibodiesnovelpathogenperipheral lymphoid organperipheral tolerancepreventresponserestrainttranscriptome
项目摘要
PROJECT SUMMARY
Not all autoreactive B cells are censored by central tolerance during their development. Thus,
mechanisms of B cell anergy are essential for the functional silencing of autoreactive B cells that exist in the
periphery in both humans and mice. However, it remains unclear why this poorly defined process of
immunological tolerance allows for the temporary retention of autoreactive B cells in the periphery given that,
under certain genetic and environmental settings, these cells can contribute to autoimmunity. Indeed, anergic
B cells can be released from their functionally inert state but requires unique circumstances (e.g., strong TLR
stimulus and highly multimerized antigen), which could presumably occur during an uncontrolled infection. As
such, we propose that autoreactive anergic B cells may serve as a reserve population able to respond to
pathogens not contained by an initial immune response and particularly for pathogens that aim to evade the
immune response through molecular mimicry of self-antigens. Accordingly, work from our lab has recently
evaluated if autoreactive B cells that are normally silenced by immune tolerance can contribute to a protective
cross-reactive antibody response. To accomplish this we used both autoimmune prone B6.Sle123 mice and
wild-type mice treated with pristane, a treatment characterized to impair tolerance and promote autoantibody
production. These mice were immunized with HIV envelope protein (Env) and immune sera was found to
neutralize tier 2 genetic subtypes of clinically relevant HIV-1, a pathogen proposed to exploit immune tolerance
in order to evade the immune response. Furthermore, from these mice we isolated Env-specific neutralizing
monoclonal antibodies that also recognize the H2A histone protein. Thus, the goal of this proposal is to use
mouse and humanized mouse models to identify the nature and mechanisms that facilitate this antibody
response by peripheral autoreactive B cells and to establish conditions that experimentally breach tolerance
and promote cross-reactive autoantibody responses by anergic B cells.
项目摘要
并不是所有的自身反应性B细胞在发育过程中都受到中枢耐受的限制。因此,在本发明中,
B细胞无反应性的机制对于自体反应性B细胞的功能性沉默是必需的,所述自体反应性B细胞存在于
人类和小鼠的外周。然而,目前还不清楚为什么这种定义不清的过程,
免疫耐受允许自身反应性B细胞暂时保留在外周,
在特定的遗传和环境条件下,这些细胞可以促进自身免疫。的确,
B细胞可以从它们的功能惰性状态释放出来,但需要独特的环境(例如,强TLR
刺激物和高度多聚化的抗原),这可能发生在不受控制的感染期间。作为
因此,我们认为自身反应性无反应性B细胞可能作为一个储备群体,能够响应
初始免疫应答不包含的病原体,特别是旨在逃避免疫应答的病原体。
通过自身抗原的分子模拟的免疫应答。因此,我们实验室的工作最近
评估通常被免疫耐受沉默的自身反应性B细胞是否有助于保护性免疫耐受。
交叉反应性抗体应答。为了实现这一点,我们使用了自身免疫易感B6.Sle123小鼠和
用降植烷处理的野生型小鼠,降植烷是一种以损害耐受性和促进自身抗体为特征的治疗方法。
生产用HIV包膜蛋白(Env)免疫这些小鼠,发现免疫血清
中和临床相关HIV-1的二级遗传亚型,这是一种被提议利用免疫耐受的病原体
以逃避免疫反应此外,从这些小鼠中,我们分离了Env特异性中和抗体。
也识别H2 A组蛋白的单克隆抗体。因此,本提案的目标是使用
小鼠和人源化小鼠模型,以鉴定促进这种抗体的性质和机制
外周自身反应性B细胞的反应,并建立实验性破坏耐受性的条件
并促进无反应性B细胞的交叉反应性自身抗体应答。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Silencing of TLM B cells by chronic HIV infection.
慢性 HIV 感染导致 TLM B 细胞沉默。
- DOI:10.1038/s41590-018-0191-2
- 发表时间:2018
- 期刊:
- 影响因子:30.5
- 作者:Agazio,AmandaE;Pelanda,Roberta;Torres,RaulM
- 通讯作者:Torres,RaulM
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Raul Martin Torres其他文献
Raul Martin Torres的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Raul Martin Torres', 18)}}的其他基金
Chronic alcohol consumption results in elevated Autotaxin levels that suppress anti-tumor immunity
长期饮酒会导致自分泌运动因子水平升高,从而抑制抗肿瘤免疫力
- 批准号:
10370159 - 财政年份:2022
- 资助金额:
$ 51.06万 - 项目类别:
Chronic alcohol consumption results in elevated Autotaxin levels that suppress anti-tumor immunity
长期饮酒会导致自分泌运动因子水平升高,从而抑制抗肿瘤免疫力
- 批准号:
10595090 - 财政年份:2022
- 资助金额:
$ 51.06万 - 项目类别:
Lysophosphatidic Acid Regulation of CD8 T cell activation and function
溶血磷脂酸对 CD8 T 细胞活化和功能的调节
- 批准号:
10116268 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Lysophosphatidic Acid Regulation of CD8 T cell activation and function
溶血磷脂酸对 CD8 T 细胞活化和功能的调节
- 批准号:
10348723 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Lysophosphatidic Acid Regulation of CD8 T cell activation and function
溶血磷脂酸对 CD8 T 细胞活化和功能的调节
- 批准号:
10574540 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Chemokine response in B cell development and function
B 细胞发育和功能中的趋化因子反应
- 批准号:
6843138 - 财政年份:2002
- 资助金额:
$ 51.06万 - 项目类别:
Antigen and lysophospholipid receptor regulation of lymphocyte development and fu
抗原和溶血磷脂受体对淋巴细胞发育和功能的调节
- 批准号:
8846018 - 财政年份:2002
- 资助金额:
$ 51.06万 - 项目类别:
相似海外基金
Multidimensional development of high-affinity anti-glycan antibodies to fight deadly bacterial infections
多维开发高亲和力抗聚糖抗体以对抗致命细菌感染
- 批准号:
10549640 - 财政年份:2023
- 资助金额:
$ 51.06万 - 项目类别:
Computational modelling and simulation of antibodies to enhance binding affinity of a potential Burkholderia pseudomallei therapeutic
抗体的计算模型和模拟,以增强潜在的鼻疽伯克霍尔德氏菌治疗剂的结合亲和力
- 批准号:
2750554 - 财政年份:2021
- 资助金额:
$ 51.06万 - 项目类别:
Studentship
Affinity Biosensors for COVID-19 Antibodies
适用于 COVID-19 抗体的亲和生物传感器
- 批准号:
61319 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Feasibility Studies
Directed Evolution of HIV Broadly Neutralizing Antibodies Using a Novel CRISPR-Engineered B cell in Vitro Affinity Maturation Platform
使用新型 CRISPR 工程 B 细胞在体外亲和力成熟平台定向进化 HIV 广泛中和抗体
- 批准号:
10013588 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Affinity maturation and property changes of single-domain antibodies through repeated immunizations.
通过重复免疫,单域抗体的亲和力成熟和性质变化。
- 批准号:
20K07009 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Rapid structure-based software to enhance antibody affinity and developability for high-throughput screening: Aiming toward total in silico design of antibodies
基于快速结构的软件可增强抗体亲和力和高通量筛选的可开发性:旨在实现抗体的全面计算机设计
- 批准号:
10603473 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
IN SILICO DESIGN OF HIGH-AFFINITY RECOMBINANT ANTIBODIES
高亲和力重组抗体的计算机模拟设计
- 批准号:
2342674 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Studentship
Strategies for generating high affinity antibodies against Gram negative bacteria
产生针对革兰氏阴性菌的高亲和力抗体的策略
- 批准号:
10117194 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Directed Evolution of HIV Broadly Neutralizing Antibodies Using a Novel CRISPR-Engineered B cell in Vitro Affinity Maturation Platform
使用新型 CRISPR 工程 B 细胞在体外亲和力成熟平台定向进化 HIV 广泛中和抗体
- 批准号:
10115604 - 财政年份:2020
- 资助金额:
$ 51.06万 - 项目类别:
Interdisciplinary protein engineering approach to design high affinity antibodies for flaviviruses
跨学科蛋白质工程方法设计黄病毒高亲和力抗体
- 批准号:
10294224 - 财政年份:2018
- 资助金额:
$ 51.06万 - 项目类别: