The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice

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. Her...

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Autores principales:	Michael Jonathan Lehrke, Michael Jeremy Shapiro, Matthew J Rajcula, Madeleine M Kennedy, Shaylene A McCue, Kay L Medina, Virginia Smith Shapiro
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	ABCB7 B cells iron Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b26e13f1acd846d4bac1d67398df6ccb
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spelling	oai:doaj.org-article:b26e13f1acd846d4bac1d67398df6ccb2021-11-11T14:23:40ZThe mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice10.7554/eLife.696212050-084Xe69621https://doaj.org/article/b26e13f1acd846d4bac1d67398df6ccb2021-11-01T00:00:00Zhttps://elifesciences.org/articles/69621https://doaj.org/toc/2050-084XIron-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 replication-induced 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.Michael Jonathan LehrkeMichael Jeremy ShapiroMatthew J RajculaMadeleine M KennedyShaylene A McCueKay L MedinaVirginia Smith ShapiroeLife Sciences Publications LtdarticleABCB7B cellsironMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ABCB7 B cells iron Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	ABCB7 B cells iron Medicine R Science Q Biology (General) QH301-705.5 Michael Jonathan Lehrke Michael Jeremy Shapiro Matthew J Rajcula Madeleine M Kennedy Shaylene A McCue Kay L Medina Virginia Smith Shapiro The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice
description	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 replication-induced 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.
format	article
author	Michael Jonathan Lehrke Michael Jeremy Shapiro Matthew J Rajcula Madeleine M Kennedy Shaylene A McCue Kay L Medina Virginia Smith Shapiro
author_facet	Michael Jonathan Lehrke Michael Jeremy Shapiro Matthew J Rajcula Madeleine M Kennedy Shaylene A McCue Kay L Medina Virginia Smith Shapiro
author_sort	Michael Jonathan Lehrke
title	The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice
title_short	The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice
title_full	The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice
title_fullStr	The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice
title_full_unstemmed	The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice
title_sort	mitochondrial iron transporter abcb7 is required for b cell development, proliferation, and class switch recombination in mice
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/b26e13f1acd846d4bac1d67398df6ccb
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The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice

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