The E3 ubiquitin ligase Itch regulates antibody levels and prevents autoimmune disease in humans and mice, yet how Itch regulates B cell fate or function is unknown. We now show that Itch directly limits B cell activity. While Itch-deficient mice displayed normal numbers of preimmune B cell populations, they showed elevated numbers of antigen-experienced B cells. Mixed bone marrow chimeras revealed that Itch acts within B cells to limit naive and, to a greater extent, germinal center (GC) B cell numbers. B cells lacking Itch exhibited increased proliferation, glycolytic capacity, and mTORC1 activation. Moreover, stimulation of these cells in vivo by WT T cells resulted in elevated numbers of GC B cells, PCs, and serum IgG. These results support a novel role for Itch in limiting B cell metabolism and proliferation to suppress antigen-driven B cell responses.
The E3 ubiquitin ligase Itch restricts antigen-driven B cell responses
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Emily K. Moser, Jennifer Roof, Joseph M. Dybas, Lynn A. Spruce, Steven H. Seeholzer, Michael P. Cancro, Paula M. Oliver; The E3 ubiquitin ligase Itch restricts antigen-driven B cell responses. J Exp Med 2 September 2019; 216 (9): 2170–2183. doi: https://doi.org/10.1084/jem.20181953
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