限制
抗原
免疫学
细胞
生物
细胞生物学
遗传学
机械工程
工程类
作者
Mukta Deobagkar‐Lele,Greg Crawford,Tanya L. Crockford,Jennifer Back,Rose Hodgson,Aneesha Bhandari,Katherine R. Bull,Richard J. Cornall
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-08-09
卷期号:9 (98)
标识
DOI:10.1126/sciimmunol.add4874
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI