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- Title
The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice.
- Authors
Lehrke, Michael Jonathan; Shapiro, Michael Jeremy; Rajcula, Matthew J.; Kennedy, Madeleine M.; McCue, Shaylene A.; Medina, Kay L.; Shapiro, Virginia Smith
- Abstract
Iron- sulfur (Fe- S) clusters are cofactors essential for the activity of numerous enzymes including DNA polymerases, helicases, and glycosylases. They are synthesized in the mitochondria as Fe- S intermediates and are exported to the cytoplasm for maturation by the mitochondrial transporter ABCB7. Here, we demonstrate that ABCB7 is required for bone marrow B cell development, proliferation, and class switch recombination, but is dispensable for peripheral B cell homeostasis in mice. Conditional deletion of ABCB7 using Mb1- cre resulted in a severe block in bone marrow B cell development at the pro- B cell stage. The loss of ABCB7 did not alter expression of transcription factors required for B cell specification or commitment. While increased intracellular iron was observed in ABCB7- deficient pro- B cells, this did not lead to increased cellular or mitochondrial reactive oxygen species, ferroptosis, or apoptosis. Interestingly, loss of ABCB7 led to replicationinduced DNA damage in pro- B cells, independent of VDJ recombination, and these cells had evidence of slowed DNA replication. Stimulated ABCB7- deficient splenic B cells from CD23- cre mice also had a striking loss of proliferation and a defect in class switching. Thus, ABCB7 is essential for early B cell development, proliferation, and class switch recombination.
- Subjects
IMMUNOGLOBULIN class switching; BONE marrow cells; DNA polymerases; DNA replication; CELL differentiation; HOMEOSTASIS; B cells
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.69621