Hang T. Nguyen, Moyi Li, Rahul Vadakath, Keirstin A. Henke, Tam C. Tran, Huifang Li, Maryam Yamadi, Sriranjani Darbha, Yandan Yang, Juraj Kabat, Anne R. Albright, Enoc Granados Centeno, James D. Phelan, Sandrine Roulland, Da Wei Huang, Michael C. Kelly, Ryan M. Young, Stefania Pittaluga, Simone Difilippantonio, Jagan R. Muppidi
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引用次数: 0
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. Muppidi and colleagues show that loss of Gα13 drives B cell lymphomas preferentially in the mesenteric lymph nodes. They find that Gα13 is required to counteract mTORC1 and Myc signaling that is driven by the availability of dietary glutamine.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.