Orchestration of B lymphoid cells and their inner myeloid by Bach.

ABSTRACT

The transcription repressor Bach2 is required for class switch recombination and somatic hypermutation of antibody genes in B cells, and proper development of effector and regulatory T cells. In addition, Bach2 and its related factor Bach1 promote B cell commitment of progenitor cells by repressing myeloid-related genes. Bach2 and the myeloid regulators C/EBPß and C/EBPα mutually repress their expression, forming a gene regulatory network (GRN) that dictates the process of lineage commitment. Bach2 forms another GRN with the plasma cell regulator Blimp-1, in which Bach2 and Blimp-1 mutually repress their expression. Since Bach2 expression is reduced in plasma cells, the repression of myeloid-related genes in B cells may be dissolved upon terminal differentiation of B cells to plasma cells. The Bach2 GRNs support the myeloid-based model of hematopoiesis. Myeloid-like characteristics suppressed or manifested in B cells by modifying differentiation trajectories of B and myeloid cells may be termed as 'inner myeloid' after the concept of 'inner fish'.