4 years ago

Allospecific Memory B Cell Responses Are Dependent on Autophagy

Z. Yue, J. Ni, P. S. Heeger, F. Nina Papavasiliou, M. Fribourg, J. S. Leventhal
Long-lived, donor-reactive memory B cells (Bmems) can produce alloantibodies that mediate transplant injury. Autophagy, an intrinsic mechanism of cell organelle/component recycling, is required for Bmem survival in infectious and model antigen systems, but whether autophagy affects alloreactive Bmem is unknown. We studied mice with an inducible yellow fluorescent protein (YFP) reporter expressed under the activation-induced cytidine deaminase (AID) promoter active in B cells undergoing germinal center reactions. Up to 12 months after allogeneic sensitization, splenic YFP+ B cells were predominantly IgD–IgM–IgG+ and expressed CD73, CD80, and PD-L2, consistent with Bmems. Labeled cells contained significantly more cells with autophagosomes and more autophagosomes per cell than unlabeled, naïve B cells. To test for a functional link, we quantified alloantibody formation in mice with B cells conditionally deficient in the requisite autophagy gene ATG7. These experiments revealed absent B cell ATG7 (1) prevented B cell autophagy, (2) inhibited secondary alloantibody responses without altering primary alloantibody formation, and (3) diminished frequencies of alloreactive Bmems. Pharmacological autophagy inhibition with 3-methyladenine had similar effects on wild-type mice. Together with new documentation of increased autophagosomes within human Bmems, our data indicate that targeting autophagy has potential for eliminating donor-reactive Bmems in transplant recipients.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/ajt.14394

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.