BPTF is essential for vaccine-induced germinal center B cell responses
Abstract
Abstract Germinal centers (GCs) are microanatomical structures in which antigen-specific B cells undergo proliferation, somatic hypermutation, and affinity-based competition to select high-affinity clones that differentiate into memory B cells and plasma cells (PCs). B cell progression through the GC is tightly regulated, and the molecular determinants that modulate GC B cell proliferation and survival are still under investigation. Here, we use a conditional deletion mouse model to demonstrate that bromodomain PHD finger transcription factor (BPTF), a subunit of the nucleosome remodeling factor chromatin remodeling complex, is required for robust GC B cell responses following vaccination. In GC B cells, Bptf loss induces a stress-like transcriptional profile and a shift toward PC identity-defining transcriptional programing, although this does not lead to accumulation of functional PCs. Rather, we show that BPTF-deficient GC B cells are prone to cell death. Cumulatively, our data demonstrate that BPTF is necessary for GC B cell maintenance and robust antigen-specific B cell responses.
Article Details
Journal Info
The Journal of Immunology
American Association of Immunologists
Authors (14)
Alexandria J Sturtz
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Birk K Evavold
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Zarifeh Heidari Rarani
University of Pittsburgh
Wafaa B Alsoussi
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Julian Q Zhou
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Hanover C Matz
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Hiromi Muramatsu
Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania
Wren Simkins
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Sameer Kumar Malladi
Katherine M McIntire
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Jishnu Das
Jackson S Turner
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,
Norbert Pardi
Ali H Ellebedy
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis , St. Louis, MO,