BPTF is essential for vaccine-induced germinal center B cell responses
Alexandria J Sturtz, Birk K Evavold, Zarifeh Heidari Rarani, Wafaa B Alsoussi, Julian Q Zhou, Hanover C Matz, Hiromi Muramatsu, Wren Simkins, Sameer Kumar Malladi, Katherine M McIntire, Jishnu Das, Jackson S Turner, Norbert Pardi, Ali H EllebedyAbstract
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.