Intrinsic differences in the initiation of B cell receptor signaling favor responses of human IgG(+) memory B cells over IgM(+) naive B cells.
Intrinsic differences in the initiation of B cell receptor signaling favor responses of human IgG(+) memory B cells over IgM(+) naive B cells.
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DOI：
10.4049/jimmunol.1102322
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Pierce SK
中科院分区：
文献类型：
--
作者：
Davey AM;Pierce SK
获得长寿记忆B细胞（MBC）对于防御许多感染性疾病至关重要。尽管它们的重要性，很少有人知道抗原（Ag）如何触发人类MBCs，即使我们的理解模型系统中的Ag激活B细胞的分子基础已经取得了相当大的进展。在这里，我们使用定量，高分辨率，活细胞成像在单细胞和单分子水平上描述人类同种型转换，IgG表达的MBC中最早的Ag驱动事件，并将其与IgM表达的幼稚B细胞中的Ag驱动事件进行比较。我们发现，在启动B细胞受体（BCR）信号传导的每个步骤中，人MBCs比幼稚B细胞更稳健，包括含Ag膜的询问，亚显微镜下BCR寡聚体的形成以及信号相关激酶的募集和激活。尽管MBC对Ag的反应很强，但它们对Fcγ RIIB介导的抑制仍然高度敏感。我们还证明，在没有Ag的情况下，MBC受体的一部分自发寡聚化和磷酸化激酶在膜上积累，并推测，提高组成性信号可能在维持MBC寿命中发挥作用。使用高分辨率成像，我们已经提供了一个描述的最早期的事件在银激活的MBCs和获得性细胞内在的差异，在人类幼稚和MBCs的BCR信号启动的证据。
The acquisition of long-lived memory B cells (MBCs) is critical for the defense against many infectious diseases. Despite their importance, little is known about how antigens (Ags) trigger human MBCs, even though our understanding of the molecular basis of Ag activation of B cells in model systems has advanced considerably. Here, we use quantitative, high-resolution, live cell imaging at the single cell and single molecule levels to describe the earliest Ag-driven events in human isotype-switched, IgG-expressing MBCs and compare them to those in IgM-expressing naïve B cells. We show that human MBCs are more robust than naïve B cells at each step in the initiation of B cell receptor (BCR) signaling, including interrogation of Ag-containing membranes, formation of sub-microscopic BCR oligomers and recruitment and activation of signaling-associated kinases. Despite their robust response to Ag, MBCs remain highly sensitive to FcγRIIB-mediated inhibition. We also demonstrate that in the absence of Ag, a portion of MBC receptors spontaneously oligomerized and phosphorylated kinases accumulated at the membrane and speculate that heightened constitutive signaling may play a role in maintaining MBC longevity. Using high-resolution imaging we have provided a description of the earliest events in the Ag activation of MBCs and evidence for acquired cell-intrinsic differences in the initiation of BCR signaling in human naïve and MBCs.
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影响因子：
5.3
作者：
Li, Q;Lau, A;Stanley, EF
通讯作者：
Stanley, EF
DOI：
10.1073/pnas.0703872104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Good, Kim L.;Tangye, Stuart G.
通讯作者：
Tangye, Stuart G.
影响因子：
32.4
作者：
Liu W;Meckel T;Tolar P;Sohn HW;Pierce SK
通讯作者：
Pierce SK
影响因子：
32.4
作者：
Carrasco, YR;Fleire, SJ;Batista, FD
通讯作者：
Batista, FD
DOI：
10.1084/jem.186.6.931
发表时间：
1997-09-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arpin C;Banchereau J;Liu YJ
通讯作者：
Liu YJ