The B cell receptor-mTOR signaling axis restricts the accumulation of lung tissue-resident memory B cells following influenza infection

However, the pathways regulating the accumulation of lung BRM cells are poorly understood. Here we show that the transcription factors NFATC1 (nuclear factor of activated T cells 1) and EGR2 (early growth response 2) repress lung BRM cell accumulation following influenza infection, whereas IKZF1 (IKAROS family zinc finger 1) enhances it.

IKZF1 restrains B cell receptor (BCR) and mTOR (mechanistic target of rapamycin) signaling and is highly expressed in lung BRM cells during their development. Lung BRM cells display reduced expression of genes associated with BCR and mTOR signaling pathways. Overexpression of a degradation-resistant form of SYK downstream of the BCR restricted lung BRM cell accumulation.