ACT-seq of murine lymphoid cells from spleen
APOBEC2 is a conserved, catalytically inactive member of the AID/APOBEC family of cytidine deaminases. Unlike other family members that edit RNA or mutate DNA, APOBEC2 functions as a DNA-binding transcriptional regulator. It is highly expressed in muscle tissue, where it maintains muscle identity by repressing non-muscle gene expression. While its role in muscle is well established, our study uncovers a previously unrecognized and essential function for APOBEC2 in the immune system.  We demonstrate that APOBEC2 is also expressed in hematopoietic cells and plays a crucial role in preserving lymphoid lineage fidelity. In mice, APOBEC2 deficiency leads to the emergence of aberrant lymphocytes with a hybrid identity, co-expressing both T cell and B cell genes and receptors (TCR and BCR), along with dual functional capacities.  Together, our findings establish APOBEC2 as a regulator of lymphoid identity, preventing inappropriate B cell programming within the T cell lineage, with direct implications for immune development and disease in both mice and humans.
APOBEC2 is a conserved, catalytically inactive member of the AID/APOBEC family of cytidine deaminases. Unlike other family members that edit RNA or mutate DNA, APOBEC2 functions as a DNA-binding transcriptional regulator. It is highly expressed in muscle tissue, where it maintains muscle identity by repressing non-muscle gene expression. While its role in muscle is well established, our study uncovers a previously unrecognized and essential function for APOBEC2 in the immune system.  We demonstrate that APOBEC2 is also expressed in hematopoietic cells and plays a crucial role in preserving lymphoid lineage fidelity. In mice, APOBEC2 deficiency leads to the emergence of aberrant lymphocytes with a hybrid identity, co-expressing both T cell and B cell genes and receptors (TCR and BCR), along with dual functional capacities.  Together, our findings establish APOBEC2 as a regulator of lymphoid identity, preventing inappropriate B cell programming within the T cell lineage, with direct implications for immune development and disease in both mice and humans.
German Cancer Research Center (DKFZ), Heidelberg, Germany