Cbl and Cbl-b control the germinal center reaction by facilitating naive B cell antigen processing
Cbl and Cbl-b control the germinal center reaction by facilitating naive B cell antigen processing
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DOI：
10.1084/jem.20191537
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发表时间：
2020-09-01
影响因子：
15.3
通讯作者：
Gu, Hua
中科院分区：
文献类型：
--
作者：
Li, Xin;Gong, Liying;Gu, Hua
幼稚B细胞和生发中心（GC） B细胞对抗原的摄取和呈递是不同的，前者即使表达低亲和力的bcr也能有效地捕获并呈递足够的抗原给T细胞，而后者在获得高亲和力的bcr后能更有效地捕获和呈递足够的抗原。我们在这里表明，抗原的摄取和加工由幼稚B细胞而不是GC B细胞依赖于Cbl和Cbl- B (Cbls)，因此控制幼稚B细胞和同源T滤泡辅助（Tfh）细胞的相互作用和GC反应的启动。Cbls介导CD79A和CD79B泛素化，分别是bcr介导的抗原内吞和内吞后对溶酶体的分选所必需的。阻断CD79A或CD79B泛素化或Cbls连接酶活性足以阻碍bcr介导的抗原加工和GC的发展。因此，Cbls通过促进幼稚B细胞抗原呈递在GC反应的进入检查点起作用。这种调节可能促进具有低亲和力BCR的幼稚B细胞募集到GCs中，从而启动亲和力成熟过程。
Antigen uptake and presentation by naive and germinal center (GC) B cells are different, with the former expressing even low-affinity BCRs efficiently capture and present sufficient antigen to T cells, whereas the latter do so more efficiently after acquiring high-affinity BCRs. We show here that antigen uptake and processing by naive but not GC B cells depend on Cbl and Cbl-b (Cbls), which consequently control naive B and cognate T follicular helper (Tfh) cell interaction and initiation of the GC reaction. Cbls mediate CD79A and CD79B ubiquitination, which is required for BCR-mediated antigen endocytosis and postendocytic sorting to lysosomes, respectively. Blockade of CD79A or CD79B ubiquitination or Cbls ligase activity is sufficient to impede BCR-mediated antigen processing and GC development. Thus, Cbls act at the entry checkpoint of the GC reaction by promoting naive B cell antigen presentation. This regulation may facilitate recruitment of naive B cells with a low-affinity BCR into GCs to initiate the process of affinity maturation.