B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.
B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.
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DOI：
10.1016/j.celrep.2022.111021
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发表时间：
2022-06-28
期刊：
影响因子：
8.8
通讯作者：
Alam, S. Munir
中科院分区：
文献类型：
--
作者：
Hossain, Md. Alamgir;Anasti, Kara;Watts, Brian;Cronin, Kenneth;Derking, Ronald;Groschel, Bettina;Kane, Advaiti Pai;Edwards, R. J.;Easterhoff, David;Zhang, Jinsong;Rountree, Wes;Ortiz, Yaneth;Saunders, Kevin;Schief, William R.;Sanders, Rogier W.;Verkoczy, Laurent;Reth, Michael;Alam, S. Munir
设计用于诱导中和抗体应答的HIV-1包膜（Env）蛋白允许研究亲和力（平衡解离常数[KD]）和动力学速率（结合/解离速率）对B细胞抗原识别的作用。目前尚不清楚B细胞活化过程中的亲和力区分是否仅基于Env蛋白结合KD，以及B细胞是否区分以不同动力学速率结合的相似亲和力的蛋白质。在这里，我们使用一组Env蛋白和表达免疫球蛋白M（IgM）B细胞受体（BCR）的拉莫斯B细胞系，对CD 4结合位点广泛中和抗体具有特异性，以研究抗原结合动力学速率对B细胞活化中早期（近端/远端信号传导）和晚期事件（BCR/抗原内化）的作用。我们的研究结果支持B细胞活化的动力学模型，其中Env蛋白亲和性鉴别不是基于总体KD，而是基于对结合速率和阈值抗原-BCR半衰期的感知。Hossain等人报告称，B细胞信号传导依赖于抗原结合结合速率，而不是总体亲和力，而抗原结合诱导的内化需要更快的结合和阈值BCR-抗原停留时间。
HIV-1 envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant [KD]) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear whether affinity discrimination during B cell activation is based solely on Env protein binding KD and whether B cells discriminate among proteins of similar affinities that bind with different kinetic rates. Here, we use a panel of Env proteins and Ramos B cell lines expressing immunoglobulin M (IgM) B cell receptors (BCRs) with specificity for CD4-binding-site broadly neutralizing antibodies to study the role of antigen binding kinetic rates on both early (proximal/distal signaling) and late events (BCR/antigen internalization) in B cell activation. Our results support a kinetic model for B cell activation in which Env protein affinity discrimination is based not on overall KD but on sensing of association rate and a threshold antigen-BCR half-life. Hossain et al. reports that B cell signaling is dependent on antigen binding association rate and not the overall affinity, while antigen binding-induced internalization requires both a faster association and a threshold BCR-antigen dwell time.
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影响因子：
9.2
作者：
Brouwer PJM;Antanasijevic A;de Gast M;Allen JD;Bijl TPL;Yasmeen A;Ravichandran R;Burger JA;Ozorowski G;Torres JL;LaBranche C;Montefiori DC;Ringe RP;van Gils MJ;Moore JP;Klasse PJ;Crispin M;King NP;Ward AB;Sanders RW
通讯作者：
Sanders RW
DOI：
10.1073/pnas.79.3.884
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DINTZIS, RZ;VOGELSTEIN, B;DINTZIS, HM
通讯作者：
DINTZIS, HM
DOI：
10.1126/science.1234150
发表时间：
2013-05-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jardine J;Julien JP;Menis S;Ota T;Kalyuzhniy O;McGuire A;Sok D;Huang PS;MacPherson S;Jones M;Nieusma T;Mathison J;Baker D;Ward AB;Burton DR;Stamatatos L;Nemazee D;Wilson IA;Schief WR
通讯作者：
Schief WR
DOI：
10.4049/jimmunol.1300770
发表时间：
2013-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen Y;Zhang J;Hwang KK;Bouton-Verville H;Xia SM;Newman A;Ouyang YB;Haynes BF;Verkoczy L
通讯作者：
Verkoczy L
影响因子：
32.4
作者：
Batista, FD;Neuberger, MS
通讯作者：
Neuberger, MS