Bach2 expression favors age-associated B cell fate choice

B cells are known for their ability to produce protective antibodies after vaccination or during infection. However, antibodies from these cells can also be disease-causing in some autoimmune disorders such as systemic lupus erythematosus (SLE), where the immune system mistakes its own cellular components for invading pathogens, causing significant tissue damage and health problems in patients. Additionally, aging limits the ability to produce antibodies to new pathogens and is in part responsible for the poor vaccination responses, higher risk of severe infection and mortality in elderly people. Interestingly, both aging and many autoimmune diseases share an increase in a type of B cell termed age-associated B cells (ABCs). Of note, ABCs are thought to play a protective role in response to parasitic and viral infections, but also seem to be responsible for both lower antibody responses with aging and the production of autoantibodies driving disease in autoimmune conditions like SLE. The signaling pathways and specific genes required to generate ABCs have only recently begun to be unraveled. This project will focus on Bach2, a type of gene, called a transcription factor, whose main role is to regulate the expression of other genes within a cell. Bach2 appears to take part in the differentiation of ABCs and this project will work to better define the role of Bach2 within these cells. Understanding how ABCs are produced may lead to treatments that both ameliorate autoimmune diseases and promote more robust protective antibody responses in the elderly.