B cell antigen receptor (BCR)-driven mechanistic connection between B cell lymphomagenesis and autoimmunity
B细胞抗原受体(BCR)驱动的B细胞淋巴瘤发生与自身免疫之间的机制联系
基本信息
- 批准号:10646137
- 负责人:
- 金额:$ 35.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAffectAffinityAntibodiesAntigensAutoantibodiesAutoantigensAutoimmunityB Cell ProliferationB-Cell ActivationB-Cell Antigen ReceptorB-Cell LymphomasB-Cell NonHodgkins LymphomaB-LymphocytesBIRC3 geneCD80 AntigensCancerousCell SurvivalCellsChromosomal translocationChronicDNADNA Double Strand BreakDataDiagnosticEtiologyExhibitsFoundationsGenomeGenomic InstabilityGenomicsGoalsHen Egg LysozymeHumanImmunityImmunizationImmunoglobulin Class SwitchingImmunoglobulin Somatic HypermutationImmunoglobulin Switch RecombinationIn VitroInfectionInjectionsLicensingLinkLymphocyteLymphomaLymphomagenesisMalignant NeoplasmsMantle Cell LymphomaMature B-LymphocyteMediatingModelingMusMutagenesisMutationNR0B2 geneNon-Hodgkin&aposs LymphomaPathogenesisPathologicPoint MutationPriceProbabilityProcessProductionProtein phosphatasePublic HealthReceptor ActivationReceptor SignalingRegulationRoleSYK geneSignal InductionSignal PathwaySignal TransductionSpleenT-LymphocyteTNF Receptor-Associated FactorsTRAF2 geneTechniquesTestingactivation-induced cytidine deaminasegenome-widehumoral immunity deficiencyin vivolymph nodesmutantnovelnovel therapeuticspathogenprognosticresponsetumorigenesis
项目摘要
PROJECT SUMMARY/ABSTRACT
Title: B cell antigen receptor (BCR)-driven mechanistic connection between B cell lymphomagenesis
and autoimmunity
Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of malignancies affecting lymphocytes.
Collectively, NHL are the fifth most common cancers in the US, and more than 90% of NHL are of B cell origin.
There are roughly equal number of T and B cells in spleen and more T cells in lymph nodes. Why are B cells
so prone to lymphomagenesis? This is probably due to B cell-specific DNA mutagenesis processes, somatic
hypermutation (SHM) and class switch recombination (CSR). SHM/CSR are initiated by activation-induced
deaminase (AID) and are required to produce high affinity isotype-switched antibodies (Abs) that are essential
for immunity against pathogens. However, B cells pay a high price for utilizing AID to generate point mutations
or DNA double-stranded breaks (DSBs) during SHM/CSR. AID is a genome mutator and, if dysregulated, can
cause genome-wide DSBs that lead to chromosomal translocations and lymphomas. Hence, AID expression is
tightly controlled and only occurs in activated B cells during infection or immunization.
B cell antigen receptor (BCR) is essential for B cell survival and for recognizing specific antigens
including self-antigens. However, signaling by the BCR alone cannot induce AID expression and CSR in vitro,
and it is unclear whether BCR activation by antigen alone can induce AID expression in vivo. Why is it such an
important question to be addressed? Because this may serve as a protective mechanism to keep self-reactive
B cells from turning cancerous. If antigen alone could induce AID expression in the absence of pathogen-
associated co-stimulation, B cells might generate harmful auto-antibody responses, given the abundance of
self-antigens in our body. Chronic activation of BCR by such self-antigens will lead to survival and proliferation
of B cells, which, together with abnormally induced AID expression, would significantly increase the likelihood
of tumorigenesis. Hence, understanding the role of BCR signaling in AID regulation is highly significant, with
important implications for autoimmunity and B cell lymphomagenesis as well as the mechanistic connection
between these two pathological conditions. In this proposal, we will elucidate what factors regulate the ability
of BCR to induce AID expression, genomic instability and lymphomagenesis in B cells.
项目总结/文摘
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Why the Outcome of Anti-Tumor Immune Responses is Heterogeneous: A Novel Idea in the Context of Immunological Heterogeneity in Cancers.
- DOI:10.1002/bies.202000024
- 发表时间:2020-10
- 期刊:
- 影响因子:0
- 作者:Wang JH
- 通讯作者:Wang JH
How the Signaling Crosstalk of B Cell Receptor (BCR) and Co-Receptors Regulates Antibody Class Switch Recombination: A New Perspective of Checkpoints of BCR Signaling.
- DOI:10.3389/fimmu.2021.663443
- 发表时间:2021
- 期刊:
- 影响因子:7.3
- 作者:Chen Z;Wang JH
- 通讯作者:Wang JH
Pharmacologic targeting of Nedd8-activating enzyme reinvigorates T-cell responses in lymphoid neoplasia.
- DOI:10.1038/s41375-023-01889-x
- 发表时间:2023-06
- 期刊:
- 影响因子:11.4
- 作者:Wang, Xiaoguang;Chen, Canping;Vuong, Dan;Rodriguez-Rodriguez, Sonia;Lam, Vi;Roleder, Carly;Wang, Jing H.;Kambhampati, Swetha;Berger, Allison;Pennock, Nathan;Torka, Pallawi;Hernandez-Ilizaliturri, Francisco;Siddiqi, Tanya;Wang, Lili;Xia, Zheng;Danilov, Alexey V.
- 通讯作者:Danilov, Alexey V.
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Jing Hong Wang其他文献
Jing Hong Wang的其他文献
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{{ truncateString('Jing Hong Wang', 18)}}的其他基金
Mechanisms of Dual Inhibition of TGFbeta/PD-L1 in HNSCC
TGFbeta/PD-L1 在 HNSCC 中的双重抑制机制
- 批准号:
10620449 - 财政年份:2022
- 资助金额:
$ 35.64万 - 项目类别:
Mechanisms of Dual Inhibition of TGFbeta/PD-L1 in HNSCC
TGFbeta/PD-L1 在 HNSCC 中的双重抑制机制
- 批准号:
10541103 - 财政年份:2022
- 资助金额:
$ 35.64万 - 项目类别:
B cell antigen receptor (BCR)-driven mechanistic connection between B cell lymphomagenesis and autoimmunity
B细胞抗原受体(BCR)驱动的B细胞淋巴瘤发生与自身免疫之间的机制联系
- 批准号:
10356472 - 财政年份:2021
- 资助金额:
$ 35.64万 - 项目类别:
Developing newly combined therapeutic strategies for mature B cell lymphoma
开发成熟 B 细胞淋巴瘤的新联合治疗策略
- 批准号:
10590693 - 财政年份:2021
- 资助金额:
$ 35.64万 - 项目类别:
Developing newly combined therapeutic strategies for mature B cell lymphoma
开发成熟 B 细胞淋巴瘤的新联合治疗策略
- 批准号:
10366505 - 财政年份:2021
- 资助金额:
$ 35.64万 - 项目类别:
Elucidating Mechanism of Immune Evasion in Head and Neck Cancers
阐明头颈癌的免疫逃避机制
- 批准号:
10392687 - 财政年份:2021
- 资助金额:
$ 35.64万 - 项目类别:
Developing newly combined therapeutic strategies for mature B cell lymphoma
开发成熟 B 细胞淋巴瘤的新联合治疗策略
- 批准号:
10412143 - 财政年份:2021
- 资助金额:
$ 35.64万 - 项目类别:
B cell antigen receptor (BCR)-driven mechanistic connection between B cell lymphomagenesis and autoimmunity
B细胞抗原受体(BCR)驱动的B细胞淋巴瘤发生与自身免疫之间的机制联系
- 批准号:
9973700 - 财政年份:2020
- 资助金额:
$ 35.64万 - 项目类别:
Mechanisms of dual inhibition of TGFbeta/PD-L1 in HNSCC
TGFbeta/PD-L1双重抑制在HNSCC中的作用机制
- 批准号:
10306373 - 财政年份:2019
- 资助金额:
$ 35.64万 - 项目类别:
Developing newly combined therapeutic strategies for mature B cell lymphoma
开发成熟 B 细胞淋巴瘤的新联合治疗策略
- 批准号:
9902383 - 财政年份:2019
- 资助金额:
$ 35.64万 - 项目类别:
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