Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB

Simon N. Willis, Julie Tellier, Yang Liao, Stephanie Trezise, Amanda Light, Kristy O'Donnell, Lee Ann Garrett-Sinha, Wei Shi, David M. Tarlinton, Stephen L. Nutt

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Abstract

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 haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-Affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation. PU.1 and SpiB regulate the expression of many components of the B cell receptor signaling pathway and the receptors for CD40L, BAFF and TLR ligands. Thus, PU.1 and SpiB enable B cells to appropriately respond to environmental cues.

Original languageEnglish
Article number1426
Number of pages14
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Cite this

Willis, S. N., Tellier, J., Liao, Y., Trezise, S., Light, A., O'Donnell, K., Garrett-Sinha, L. A., Shi, W., Tarlinton, D. M., & Nutt, S. L. (2017). Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB. Nature Communications, 8(1), [1426]. https://doi.org/10.1038/s41467-017-01605-1