The transcription repressors Bach2 and Bach1 promote B cell development by repressing the myeloid program

• Published in: Nature immunology Vol. 15; no. 12; pp. 1171 - 1180
• Main Authors: Itoh-Nakadai, Ari, Hikota, Reina, Muto, Akihiko, Kometani, Kohei, Watanabe-Matsui, Miki, Sato, Yuki, Kobayashi, Masahiro, Nakamura, Atsushi, Miura, Yuichi, Yano, Yoko, Tashiro, Satoshi, Sun, Jiying, Ikawa, Tomokatsu, Ochiai, Kyoko, Kurosaki, Tomohiro, Igarashi, Kazuhiko
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2014; Nature Publishing Group
• Subjects: 13/109; 13/31; 38/61; 38/77; 42; 631/80; Animals; B cells; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - metabolism; Biomedicine; Cell Differentiation - physiology; Cell Lineage; Cell Separation; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Flow Cytometry; Gene Expression Regulation - physiology; Genetic aspects; Genetic research; Genetic transcription; Immunology; Infectious Diseases; Lymphoid Progenitor Cells - cytology; Lymphoid Progenitor Cells - metabolism; Lymphopoiesis - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Precursor Cells, B-Lymphoid - cytology; Precursor Cells, B-Lymphoid - metabolism; Properties; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription factors
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3024

The role of the repressors Bach1 and Bach2 in early B cell development is unclear. Igarashi and colleagues have now found these Bach factors directly repress various myeloid genes in common lymphoid progenitors to restrict a B cell lineage fate. Mature lymphoid cells express the transcription repressor Bach2, which imposes regulation on humoral and cellular immunity. Here we found critical roles for Bach2 in the development of cells of the B lineage, commencing from the common lymphoid progenitor (CLP) stage, with Bach1 as an auxiliary. Overexpression of Bach2 in pre-pro-B cells deficient in the transcription factor EBF1 and single-cell analysis of CLPs revealed that Bach2 and Bach1 repressed the expression of genes important for myeloid cells ('myeloid genes'). Bach2 and Bach1 bound to presumptive regulatory regions of the myeloid genes. Bach2 hi CLPs showed resistance to myeloid differentiation even when cultured under myeloid conditions. Our results suggest that Bach2 functions with Bach1 and EBF1 to promote B cell development by repressing myeloid genes in CLPs.