Allospecific Memory B Cell Responses Are Dependent on Autophagy

M. Fribourg, J. Ni, F. Nina Papavasiliou, Z. Yue, P. S. Heeger, J. S. Leventhal

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)102-112
Number of pages11
JournalAmerican Journal of Transplantation
Volume18
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • B cell biology
  • alloantibody
  • alloantigen
  • basic (laboratory) research/science
  • cellular biology
  • desensitization
  • heart transplantation/cardiology
  • immunobiology
  • rejection: antibody-mediated (ABMR)

Fingerprint

Dive into the research topics of 'Allospecific Memory B Cell Responses Are Dependent on Autophagy'. Together they form a unique fingerprint.

Cite this