FIP200 regulates plasma B cell differentiation via mitochondrial and heme homeostasis
Little is known about the role of autophagy in the human humoral immune system. Here, we found that in B cells, genetic ablation of FIP200, a mammalian metabolic sensor that regulates autophagy in response to a range of stimuli, led to diminished humoral immune responses in mice. FIP200-deficient B cells displayed decreased differentiation into plasma cells, as well as mitochondrial dysfunction, alterations in heme biosynthesis, and significant cell death. Notably, the addition of heme was sufficient to rescue plasma cell differentiation of FIP200-deficient B cells. Thus, FIP200 determines B cell fates by controlling mitophagy and metabolic reprogramming.
Authors
- John E. Warner (ORCID: https://orcid.org/0009-0001-1043-1643)
- Ian G. Ganley (ORCID: https://orcid.org/0000-0003-1481-9407)
- Zhenfei Xie (ORCID: https://orcid.org/0009-0006-9341-4721)
- Usha Nair (ORCID: https://orcid.org/0000-0002-1927-6889)
- Maria Bottermann (ORCID: https://orcid.org/0000-0002-8178-100X)
- Andrew Filby (ORCID: https://orcid.org/0000-0001-9078-4360)
- Paula Maldonado Villavicencio (ORCID: https://orcid.org/0009-0008-2321-9669)
- Stephanie R. Weldon (ORCID: https://orcid.org/0000-0001-5384-9946)
- Alison E. Ringel (ORCID: https://orcid.org/0000-0002-6451-9376)
- Xiaotie Liu (ORCID: https://orcid.org/0009-0001-5759-3498)
- Facundo D. Batista (ORCID: https://orcid.org/0000-0002-1130-9463)
- Liling Xu (ORCID: https://orcid.org/0009-0001-4477-5380)
Institutions
- Harvard University (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- MRC Protein Phosphorylation and Ubiquitylation Unit (GB)
- Massachusetts Institute of Technology (US)
- Newcastle University (GB)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1084/jem.20250535
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00