Antibodies are exceptionally versatile molecules with remarkable flexibility in their binding properties. Their natural targets range from small-molecule toxins, across viruses of different sizes, to bacteria and large multicellular parasites. The molecular determinants bound by antibodies include proteins, peptides, carbohydrates, nucleic acids, lipids and even synthetic molecules that have never existed in nature. Membrane-anchored antibodies also serve as receptors on the surface of the B cells that produce them. Despite recent structural insights, there is still no unifying molecular mechanism to explain how antibody targets (antigens) trigger the activation of these B-cell receptors (BCRs). After cognate antigen encounter, somatic hypermutation and class-switch recombination allow BCR affinity maturation and immunoglobulin class-specific responses, respectively. This raises the fundamental question of how one receptor activation mechanism can accommodate a plethora of variant receptors and ligands, and how it can ensure that individual B cells remain responsive to antigen after somatic hypermutation and class switching. There is still no definite answer. Here we give a brief historical account of the different models proposed to explain BCR triggering and discuss their merit in the context of the current knowledge of the structure of BCRs, their dynamic membrane distribution, and recent biochemical and cell biological insights.

抗体是用途极其广泛的分子，其结合特性具有显着的灵活性。它们的天然目标范围从小分子毒素、不同大小的病毒到细菌和大型多细胞寄生虫。抗体结合的分子决定簇包括蛋白质、肽、碳水化合物、核酸、脂质甚至自然界中从未存在过的合成分子。膜锚定抗体还充当产生它们的 B 细胞表面的受体。尽管最近有了结构见解，但仍然没有统一的分子机制来解释抗体靶标（抗原）如何触发这些 B 细胞受体 (BCR) 的激活。遇到同源抗原后，体细胞超突变和类别转换重组分别允许 BCR 亲和力成熟和免疫球蛋白类别特异性反应。这就提出了一个基本问题：一种受体激活机制如何适应大量的变异受体和配体，以及如何确保个体 B 细胞在体细胞超突变和类别转换后保持对抗原的反应。目前还没有明确的答案。在这里，我们对为解释 BCR 触发而提出的不同模型进行了简要的历史描述，并在 BCR 结构、动态膜分布以及最近的生化和细胞生物学见解的当前知识背景下讨论了它们的优点。