Department of Physics and Astronomy, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2024 Sep 24;121(39):e2320537121. doi: 10.1073/pnas.2320537121. Epub 2024 Sep 20.
To respond and adapt, cells use surface receptors to sense environmental cues. While biochemical signal processing inside the cell is studied in depth, less is known about how physical processes during cell-cell contact impact signal acquisition. New experiments found that fast-evolving immune B cells in germinal centers (GCs) apply force to acquire antigen clusters prior to internalization, suggesting adaptive benefits of physical information extraction. We present a theory of stochastic antigen transfer and show that maximizing information gain via physical extraction can explain the dramatic phenotypic transition from naive to GC B cells-attenuated receptor signaling, enhanced force usage, and decentralized contact architecture. Our model suggests that binding-lifetime measurement and physical extraction serve as complementary modes of antigen recognition, greatly extending the dynamic range of affinity discrimination when combined. This physical-information framework further predicts that the optimal size of receptor clusters decreases as affinity improves, rationalizing the use of a multifocal synaptic pattern seen in GC B cells. By linking extraction dynamics to selection fidelity via discriminatory performance, we propose that cells may physically enhance information acquisition to sustain adaptive evolution.
为了做出反应和适应,细胞利用表面受体来感知环境线索。虽然细胞内的生化信号处理已经被深入研究,但对于细胞间接触过程中的物理过程如何影响信号获取却知之甚少。新的实验发现,生发中心(GC)中快速进化的免疫 B 细胞在内化之前会施加力来获取抗原簇,这表明物理信息提取具有适应性优势。我们提出了一个关于随机抗原转移的理论,并表明通过物理提取最大化信息增益可以解释从幼稚到 GC B 细胞的戏剧性表型转变——减弱受体信号,增强力的使用,以及分散的接触结构。我们的模型表明,结合寿命测量和物理提取作为互补的抗原识别模式,当结合使用时,大大扩展了亲和力区分的动态范围。这个物理信息框架进一步预测,受体簇的最佳大小随着亲和力的提高而减小,这合理地解释了在 GC B 细胞中观察到的多焦点突触模式的使用。通过通过区分性能将提取动力学与选择保真度联系起来,我们提出细胞可能通过物理增强信息获取来维持适应性进化。