title: Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes.
abstract: The development, homeostasis, and function of B lymphocytes involve multiple rounds of B-cell receptor (BCR)-controlled proliferation and prolonged maintenance. We analyzed the role of transcription factor Zfx, a recently identified regulator of hematopoietic stem cell maintenance, in B-cell development and homeostasis. Panhematopoietic or B cell-specific deletion of Zfx in the bone marrow blocked B-cell development at the pre-BCR selection checkpoint. Zfx deficiency in peripheral B cells caused accelerated B-cell turnover, depletion of mature recirculating B cells, and delayed T-dependent antibody responses. In addition, the numbers and function of B-1 cell lineage were reduced. Zfx-deficient B cells showed normal proximal BCR signaling, but impaired BCR-induced proliferation and survival in vitro. This was accompanied by aberrantly enhanced and prolonged integrated stress response and by delayed induction of cyclin D2 and Bcl-xL proteins. Thus, Zfx restrains the stress response and couples antigen receptor signaling to cell expansion and maintenance during B-cell development and peripheral homeostasis. These results identify a novel transcriptional regulator of the B-cell lineage and highlight the common genetic control of stem cell maintenance and lymphocyte homeostasis.
authors.affiliation: Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Teresita L
authors.initials: TL
authors.lastname: Arenzana
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith-Raska
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis