2024年7月18日，美国国家癌症研究所Jagan R. Muppidi和美国雷多斯生物医学研究中心Simone Difilippantonio研究组在《自然—免疫学》杂志发表论文，报道发现Gα13限制粘膜生发中心的营养驱动增殖。

研究团队发现Gα13缺失通过增加mTORC1信号和Myc蛋白表达来促进生发中心反应，特别是在肠系膜淋巴结(mLN)中。缺乏Gα13生发中心B细胞(GCBs)在肠系膜淋巴结中的竞争优势，不依赖于T细胞的帮助或肠道微生物群。相反，缺乏Gα13的GCBs选择性地依赖于膳食营养素，这可能是因为它们更容易进入肠道淋巴系统。

具体来说，该团队发现饮食来源的谷氨酰胺，支持肠系膜淋巴结中Gα13缺陷GCBs的增殖和Myc表达。因此，生发中心限制了饮食中谷氨酰胺对粘膜组织生发中心动力学的影响。Gα13通路突变参与这些过程，促进侵袭性淋巴瘤的肠向性。

据介绍，在粘膜部位形成的生发中心(GCs)暴露于肠道来源的因素，这些因素有可能影响独立于抗原受体驱动的选择过程的体内平衡。G蛋白Gα13将B细胞限制在生发中心，限制生发中心源性淋巴瘤的发展。

附：英文原文

Title: Gα13 restricts nutrient driven proliferation in mucosal germinal centers

Author: Nguyen, Hang T., Li, Moyi, Vadakath, Rahul, Henke, Keirstin A., Tran, Tam C., Li, Huifang, Yamadi, Maryam, Darbha, Sriranjani, Yang, Yandan, Kabat, Juraj, Albright, Anne R., Centeno, Enoc Granados, Phelan, James D., Roulland, Sandrine, Huang, Da Wei, Kelly, Michael C., Young, Ryan M., Pittaluga, Stefania, Difilippantonio, Simone, Muppidi, Jagan R.

Issue&Volume: 2024-07-18

Abstract: Germinal centers (GCs) that form in mucosal sites are exposed to gut-derived factors that have the potential to influence homeostasis independent of antigen receptor-driven selective processes. The G-protein Gα13 confines B cells to the GC and limits the development of GC-derived lymphoma. We discovered that Gα13-deficiency fuels the GC reaction via increased mTORC1 signaling and Myc protein expression specifically in the mesenteric lymph node (mLN). The competitive advantage of Gα13-deficient GC B cells (GCBs) in mLN was not dependent on T cell help or gut microbiota. Instead, Gα13-deficient GCBs were selectively dependent on dietary nutrients likely due to greater access to gut lymphatics. Specifically, we found that diet-derived glutamine supported proliferation and Myc expression in Gα13-deficient GCBs in the mLN. Thus, GC confinement limits the effects of dietary glutamine on GC dynamics in mucosal tissues. Gα13 pathway mutations coopt these processes to promote the gut tropism of aggressive lymphoma.

DOI: 10.1038/s41590-024-01910-0

Source: https://www.nature.com/articles/s41590-024-01910-0