Evolution of Adaptive Immunity
Evolution of Adaptive Immunity
批准号:
10376815
负责人:
Martin F Flajnik
金额:
$38.63万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-07-15 至 2024-03-31
关键词:
AdoptedAdultAffinityAmphibiaAnimalsAntibodiesAntibody ResponseAntigen PresentationAntigen ReceptorsAntigen-Presenting CellsAntigensAreaAutoimmunityB-Lymphocyte SubsetsB-LymphocytesBacteriaBindingBinding SitesBirdsBloodCarbohydratesCellsCommunicable DiseasesCrystallizationDataDendritic CellsDevelopmentEvolutionFishesFollicular Dendritic CellsGenesGrowthHistocompatibility Antigens Class IIHumanHumoral ImmunitiesImmuneImmune responseImmune systemImmunityImmunizationImmunoglobulin GenesImmunoglobulin MImmunoglobulinsImmunologyJawLampreysLicensingLicensing FactorLightLymphocyteLymphoid TissueMajor Histocompatibility ComplexMalignant NeoplasmsMalpighian corpusclesMammalsModelingMovementMucosal ImmunityMusNewborn AnimalsOsteichthyesPhenotypeRanaReptilesResearchSharkSpecificityStructureSurfaceT-Cell ReceptorT-LymphocyteTestingTimeTissuesTumor Necrosis Factor-BetaVertebratesWorkadaptive immune responseadaptive immunitybasechemokinecold blooded vertebratecomparativefightingjuvenile animalprospectiveresponse
中文摘要
摘要
对非哺乳动物脊椎动物(鱼、两栖动物、爬行动物和鸟类)的研究提供了
获得性免疫的基本发现,特别是关于淋巴细胞谱系,起源
主要组织相容性复合体(MHC)、粘膜免疫和抗原受体。从…
我们在鲨鱼身上所做的工作,鲨鱼是最古老的脊椎动物,具有免疫球蛋白,T细胞
受体和MHC,我们假设哺乳动物B1细胞范式可以在
新生和幼年动物。鲨鱼也有结合位点不变的抗体(生殖系-
联合基因编码抗体),这些抗体在分泌型B细胞中表达,但在幼稚B细胞中不表达
细胞。抗体被模拟成有一个不寻常的结合部位,它结合到自己的组织和
细菌,它被认为是哺乳动物中B1衍生抗体的模型。一秒钟
鲨鱼B细胞具有独特的免疫球蛋白谱(也是类B1,N区很少)的波
此外)形成新生的脾白髓,也被提议为所有人的范例
脊椎动物,我们将在老鼠和两栖动物身上进行测试。关于体液免疫反应,
众所周知,非哺乳动物脊椎动物的抗体亲和力较差,成熟程度较低。
而且似乎缺乏滤泡树突状细胞(FDC);因此其机制如何自然
抗原被提呈给B细胞的情况还知之甚少。我们重新鉴定了一种呈现抗原的
青蛙细胞(APC),表达高水平的MHC-II类,但仍提供天然抗原
免疫后较晚在B细胞滤泡中心的表面。我们假设
这些抗原前体细胞具有“双重功能”,将抗原递呈给T细胞和B细胞。我们的数据
提示T细胞在反应早期被这些APC刺激,然后被激活的T细胞
细胞许可APC停止降解抗原,上调B细胞趋化因子(CXCL13),以及
进入卵泡,将抗原呈递给特定的B细胞。我们假设这个细胞代表
冷血脊椎动物体液反应的范例,以及传统的
哺乳动物树突状细胞可以呈现这种“双重功能”表型,特别是免疫反应。
英文摘要
SUMMARY
Studies of nonmammalian vertebrates (fish, amphibians, reptiles, and birds) have provided
essential discoveries in adaptive immunity, especially regarding lymphocyte lineages, origins of
the major histocompatibility complex (MHC), mucosal immunity, and antigen receptors. From
work that we have done in sharks, the oldest living vertebrates with immunoglobulins, T cell
receptors and the MHC, we hypothesize that the mammalian B1 cell paradigm is operable in
neonatal and young animals. Sharks also have antibodies with invariant binding sites (germline-
joined gene-encoded antibodies), which are expressed in secretory B cells but not in naïve B
cells. The antibody is modeled to have an unusual binding site, it binds to self tissues and
bacteria, and it is proposed to be a model for B1-derived antibodies in mammals. A second
wave of shark B cells with a unique immunoglobulin repertoire (also B1-like, with little N-region
addition) forms the nascent splenic white pulp, also proposed to be the paradigm for all
vertebrates, which we will test in mice and amphibians. Regarding humoral immune responses,
it is well known that nonmammalian vertebrates have poor affinity maturation of the antibody
response and seem to lack follicular dendritic cells (FDC); thus the mechanism of how native
antigen is presented to B cells is poorly understood. We have re-identified an antigen presenting
cell (APC) in frogs that expresses high levels of MHC class II, and yet presents native antigen
on its surface in the center of B cell follicles relatively late after immunization. We hypothesize
that these APC perform a `double-duty,' presenting antigen to both T cells and B cells. Our data
suggest that T cells are stimulated by these APC early in a response, and then the activated T
cells license the APC to stop degrading antigen, upregulate B cell chemokines (cxcl13), and
enter the follicle to present antigen to specific B cells. We hypothesize that this cell represents
the paradigm for humoral responses in cold-blooded vertebrates, and that conventional
mammalian DC can take on this `double-duty' phenotype in particular immune responses.
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DOI:
10.1016/j.molimm.2020.10.003
发表时间:
2020-12
期刊:
Molecular immunology
影响因子:
3.6
作者:
[Almeida T, Gaigher A, Muñoz-Mérida A, Neves F, Castro LFC, Flajnik MF, Ohta Y, Esteves PJ, Veríssimo A]
通讯作者:
Veríssimo A
Prof. Dr. Jan Klein (1936-2023).
Jan Klein 教授、博士(1936-2023)。
DOI:
10.1007/s00251-023-01317-5
发表时间:
2023
期刊:
Immunogenetics
影响因子:
3.2
作者:
[Bontrop,Ronald, Flajnik,Martin, O'Huigin,ColmS, Kasahara,Masanori]
通讯作者:
Kasahara,Masanori
DOI:
10.1093/molbev/msad262
发表时间:
2023-12-01
期刊:
MOLECULAR BIOLOGY AND EVOLUTION
影响因子:
10.7
作者:
[Verissimo, Ana, Castro, L. Filipe C., Munoz-Merida, Antonio, Almeida, Tereza, Gaigher, Arnaud, Neves, Fabiana, Flajnik, Martin F., Ohta, Yuko]
通讯作者:
Ohta, Yuko
Masanori Kasahara: Long-standing Immunogenetics co-editor steps down.
Masanori Kasahara:长期担任《免疫遗传学》联合编辑的辞职。
DOI:
10.1007/s00251-022-01265-6
发表时间:
2022
期刊:
Immunogenetics
影响因子:
3.2
作者:
[Flajnik,MartinF]
通讯作者:
Flajnik,MartinF
DOI:
10.1073/pnas.2318995121
发表时间:
2024-01-16
期刊:
Proceedings of the National Academy of Sciences of the United States of America
影响因子:
11.1
作者:
[]
通讯作者:
共 6 条
Evolution of Adaptive Immunity
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批准号:9760130
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项目类别:
-
资助金额:$25.75万
-
财政年份:2013
-
负责人:Martin F Flajnik
-
依托单位:
Evolution of Adaptive Immunity
-
批准号:9899205
-
项目类别:
-
资助金额:$38.63万
-
财政年份:2013
-
负责人:Martin F Flajnik
-
依托单位:
Evolution of Adaptive Immunity
-
批准号:8578698
-
项目类别:
-
资助金额:$31.97万
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财政年份:2013
-
负责人:Martin F Flajnik
-
依托单位:
Evolution of Adaptive Immunity
-
批准号:8697164
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项目类别:
-
资助金额:$31.97万
-
财政年份:2013
-
负责人:Martin F Flajnik
-
依托单位:
Evolution of Adaptive Immunity
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批准号:8848970
-
项目类别:
-
资助金额:$13.05万
-
财政年份:2013
-
负责人:Martin F Flajnik
-
依托单位:
Ontogeny and Phylogeny of the MHC
-
批准号:7921769
-
项目类别:
-
资助金额:$7.73万
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财政年份:2009
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负责人:Martin F Flajnik
-
依托单位:
Evolution of Adaptive Immunity
-
批准号:7892029
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项目类别:
-
资助金额:$3.77万
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财政年份:2009
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负责人:Martin F Flajnik
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依托单位:
Evolution of Adaptive Immunity
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批准号:7893971
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项目类别:
-
资助金额:$7.07万
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财政年份:2009
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负责人:Martin F Flajnik
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依托单位:
Highly Stable, Anthrax-specific Shark Antibody Fragment
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批准号:6771109
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项目类别:
-
资助金额:$26.32万
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财政年份:2003
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负责人:Martin F Flajnik
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依托单位:
Highly Stable, Anthrax-specific Shark Antibody Fragment
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批准号:6675141
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项目类别:
-
资助金额:$27.53万
-
财政年份:2003
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负责人:Martin F Flajnik
-
依托单位:
PILOT--FUNCTION OF J CHAIN AND SECRETORY TAIL IN IMMUNOGLOBULIN BIOSYNTHESIS
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批准号:6301423
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项目类别:
-
资助金额:$3.55万
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财政年份:2000
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负责人:Martin F Flajnik
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依托单位:
PILOT--FUNCTION OF J CHAIN AND SECRETORY TAIL IN IMMUNOGLOBULIN BIOSYNTHESIS
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批准号:6442541
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项目类别:
-
资助金额:$7.35万
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财政年份:2000
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负责人:Martin F Flajnik
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依托单位:
PILOT--FUNCTION OF J CHAIN AND SECRETORY TAIL IN IMMUNOGLOBULIN BIOSYNTHESIS
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批准号:6495659
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项目类别:
-
资助金额:$7.35万
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财政年份:2000
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负责人:Martin F Flajnik
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依托单位:
PILOT--FUNCTION OF J CHAIN AND SECRETORY TAIL IN IMMUNOGLOBULIN BIOSYNTHESIS
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批准号:6106296
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项目类别:
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资助金额:$3.55万
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财政年份:1999
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负责人:Martin F Flajnik
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依托单位:
PILOT--FUNCTION OF J CHAIN AND SECRETORY TAIL IN IMMUNOGLOBULIN BIOSYNTHESIS
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批准号:6271167
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项目类别:
-
资助金额:$3.62万
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财政年份:1998
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负责人:Martin F Flajnik
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依托单位:
PILOT--FUNCTION OF J CHAIN AND SECRETORY TAIL IN IMMUNOGLOBULIN BIOSYNTHESIS
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批准号:6239586
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项目类别:
-
资助金额:$7.19万
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财政年份:1997
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负责人:Martin F Flajnik
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依托单位:
EVOLUTION OF ADAPTIVE IMMUNITY
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批准号:2283255
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项目类别:
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资助金额:$26.13万
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财政年份:1995
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负责人:Martin F Flajnik
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依托单位:
EVOLUTION OF ADAPTIVE IMMUNITY
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批准号:6044119
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项目类别:
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资助金额:$25.16万
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财政年份:1991
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负责人:Martin F Flajnik
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依托单位:
Evolution of Adaptive Immunity
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批准号:6437079
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项目类别:
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资助金额:$33.41万
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财政年份:1991
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负责人:Martin F Flajnik
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依托单位:
EVOLUTION OF ADAPTIVE IMMUNITY
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批准号:2791775
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项目类别:
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资助金额:$24.51万
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财政年份:1991
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负责人:Martin F Flajnik
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依托单位:
海外基金