B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell–specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.
Nagisa Sakurai, Manami Maeda, Sung-Uk Lee, Yuichi Ishikawa, Min Li, John C. Williams, Lisheng Wang, Leila Su, Mai Suzuki, Toshiki I. Saito, Shigeru Chiba, Stefano Casola, Hideo Yagita, Julie Teruya-Feldstein, Shinobu Tsuzuki, Ravi Bhatia, Takahiro Maeda
LRF regulates B cell lineage fate.