Bach2 regulates B cell survival to maintain germinal centers and promote B cell memory

The transcription factor Bach2 serves as a crucial regulator of the germinal center (GC) reaction, which is required for production of high-affinity antibodies and establishment of long-lived B cell memory. However, the stage at which Bach2 controls the GC programs and the precise mechanism underlying these processes remain poorly understood. In this study, we show that genetic ablation of Bach2 in GC B cells of mice impairs their survival and maintenance, and memory B cell formation. These defects can be rescued by enforced expression of anti-apoptotic gene Bcl2. As expected, Bach2-deficient GC B cells are defective in antibody affinity maturation, but have normal somatic hyper mutation and class switch recombination of immunoglobulin genes. Mechanistically, Bach2 controls the GC programs by directly repressing pro-apoptotic gene Bim and a set of genes involved in cell stress response and metabolic processes. Thus, our work reveals the precise roles of Bach2 in the GC biology, and demonstrates that Bach2 acts as a crucial survival regulator of GC B cells, providing a key mechanism underlying GC B maintenance and B cell memory formation.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

The transcription factor Bach2 plays a crucial role in regulating the germinal center (GC) reaction and is involved in the survival and maintenance of GC B cells and memory B cell formation. Bach2 controls GC programs by repressing pro-apoptotic gene Bim and genes related to cell stress response and metabolic processes.