The Ets-family transcription factors PU.1 and SpiB are redundantly required by mature B cells to sense and respond to environmental cues. Mus musculus

Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands and microbial products. Ets-family transcription factors regulate many aspects of hematopoiesis, although their roles in humoral immunity have proven difficult to decipher, potentially due to redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells are unable to respond protein antigen, preventing germinal center formation and high-affinity antibody production. Mutant B cells also showed impaired survival following engagement of the CD40 and TLR pathways, but paradoxically enhanced plasma cell differentiation. PU.1 and SpiB control the expression of many components of the BCR signaling pathway and the receptors for CD40L, BAFF and toll ligands. Thus PU.1 and SpiB function enables B cells to appropriately respond to environmental cues. Overall design: Transcriptional profiling of PU.1-/- and SpiB-/- activated B cells using RNA sequencing