Grant: Project Grant

B cells are the key component of our immune system, and are responsible for antibody production in response to infections. B cells are continuously produced in our bone marrow throughout life from a small population of hematopoietic stem cells. Disruptions in B cell development can lead to life-threatening disorders including immunodeficiencies and leukemias. Recently we and others identified MYSM1 as an essential protein for normal B cell production in both mice and humans. MYSM1 is a DNA binding protein that regulates gene activity during the process of B cell differentiation from stem cells. In this work we propose to identify the genes regulated by MYSM1 and characterize the mechanisms of MYSM1 activity during B cell differentiation. The role of MYSM1 in B cell cancers, including leukemias and lymphomas, will also be addressed, using mouse as a model. The work is expected to advance our understanding of B cells, and the biology of the bone marrow and the immune system. In the long-term this may lead to a better understanding and management of diseases involving B cell dysfunction.