Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
J Exp Med. 2011 Jun 6;208(6):1243-52. doi: 10.1084/jem.20102477. Epub 2011 May 16.
The germinal center (GC) reaction is essential for the generation of the somatically hypermutated, high-affinity antibodies that mediate adaptive immunity. Entry into the GC is limited to a small number of B cell clones; however, the process by which this limited number of clones is selected is unclear. In this study, we demonstrate that low-affinity B cells intrinsically capable of seeding a GC reaction fail to expand and become activated in the presence of higher-affinity B cells even before GC coalescence. Live multiphoton imaging shows that selection is based on the amount of peptide-major histocompatibility complex (pMHC) presented to cognate T cells within clusters of responding B and T cells at the T-B border. We propose a model in which T cell help is restricted to the B cells with the highest amounts of pMHC, thus allowing for a dynamic affinity threshold to be imposed on antigen-binding B cells.
生发中心（GC）反应对于产生体细胞超突变、高亲和力的抗体介导适应性免疫至关重要。进入 GC 受到限制，只有少数 B 细胞克隆能够进入；然而，目前尚不清楚这些有限数量的克隆是如何被选择的。在这项研究中，我们证明了低亲和力 B 细胞本身就有能力启动 GC 反应，但在 GC 融合之前，即使存在高亲和力 B 细胞，它们也无法扩增并被激活。活细胞多光子成像显示，选择基于在 T 细胞和 B 细胞反应簇中，与 T 细胞受体（TCR）结合的肽-主要组织相容性复合物（pMHC）的数量。我们提出了一个模型，即 T 细胞辅助作用仅限于具有最高量 pMHC 的 B 细胞，从而可以对抗原结合的 B 细胞施加动态亲和力阈值。
