# Regulation of B cell development by ABCB7

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2021 · $238,500

## Abstract

Iron homeostasis is critical for basic cellular functions and iron is used as a co-factor by many proteins
that regulate transcription, proliferation and survival. Free iron is toxic to cells. Thus, iron homeostasis is
tightly regulated. ABCB7 is an integral membrane protein found on mitochondrial inner membranes that
belongs to the ABC (ATP-binding cassette) family of transporters. ABCB7 transports Fe-S-glutathione
intermediates from the mitochondria to the cytoplasm for incorporation into ISCs (iron sulfur clusters).
Inducible deletion of ABCB7 in Mx1-cre ABCB7 conditional knockout (cKO) mice resulted in rapid
hematopoietic failure with multi-lineage defects in hematopoiesis. However, the function of ABCB7 in specific
hematopoietic lineages has not been examined. We find that both mb1-cre ABCB7 conditional knockout (cKO)
mice and CD2-icre ABCB7 cKO mice exhibit a severe block in B cell development with almost no IgM+
immature B cells produced. Deletion of ABCB7 using CD19-cre or CD23-cre had no effect on B cell
development or peripheral B cell homeostasis, indicating a specific requirement for ABCB7 early in B cell
development and demonstrating that ABCB7 is not simply required for survival. In mb1-cre or CD2-icre
ABCB7 cKO mice, there is a decrease in B cell progenitors which express intracellular µHC, and those present
are unable to downregulate the surrogate light chain genes. Iron is a co-factor for many enzymes which
regulate chromatin accessibility, including the Tet family of dioxygenases and most of the histone lysine
demethylases (KDMs). Thus, the absence of ABCB7 may disrupt the function of these enzymes, altering the
ability to appropriately regulate chromatin accessibility as B lymphocytes progress through key developmental
checkpoints. We hypothesize that disruption of iron homeostasis by deletion of ABCB7 in B cell progenitors
leads to a block in their development through dysregulation of iron-dependent chromatin-modifying enzymes,
which will be examined in this proposal.

## Key facts

- **NIH application ID:** 10149111
- **Project number:** 1R21AI157328-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Virginia Smith Shapiro
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $238,500
- **Award type:** 1
- **Project period:** 2021-03-17 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149111

## Citation

> US National Institutes of Health, RePORTER application 10149111, Regulation of B cell development by ABCB7 (1R21AI157328-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10149111. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*