Dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome is characterized by a failure of the germinal center response, a process involving the proliferation and positive selection of antigen-specific B cells. Here, we describe how DOCK8-deficient B cells are blocked at a light-zone checkpoint in the germinal centers of immunized mice, where they are unable to respond to T cell–dependent survival and selection signals and consequently differentiate into plasma cells or memory B cells. Although DOCK8-deficient B cells can acquire and present antigen to initiate activation of cognate T cells, integrin up-regulation, B cell–T cell conjugate formation, and costimulation are insufficient for sustained B cell and T cell activation when antigen availability is limited. Our findings provide an explanation for the failure of the humoral response in DOCK8 immunodeficiency syndrome and insight into how the level of available antigen modulates B cell–T cell cross-talk to fine-tune humoral immune responses and immunological memory.

中文翻译：

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当抗原有限时，B 细胞需要 DOCK8 来引发和整合 T 细胞帮助


胞质分裂专用者 8 (DOCK8) 免疫缺陷综合征的特征是生发中心反应失败，该过程涉及抗原特异性 B 细胞的增殖和阳性选择。在这里，我们描述了 DOCK8 缺陷 B 细胞如何在免疫小鼠生发中心的光区检查点被阻断，它们无法对 T 细胞依赖性生存和选择信号做出反应，从而分化为浆细胞或记忆 B 细胞细胞。尽管 DOCK8 缺陷的 B 细胞可以获得并呈递抗原以启动同源 T 细胞的激活，但当抗原可用性有限时，整合素上调、B 细胞-T 细胞缀合物形成和共刺激不足以持续激活 B 细胞和 T 细胞。我们的研究结果为 DOCK8 免疫缺陷综合征中体液反应失败提供了解释，并深入了解了可用抗原的水平如何调节 B 细胞-T 细胞交叉对话以微调体液免疫反应和免疫记忆。