Lung tissue-resident memory B (BRM) cells are important in establishing protective immunity against respiratory pathogens. 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 after 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. Conversely, inhibition of mTOR using rapamycin reduced NFATC1 and EGR2 expression and promoted lung BRM cell accumulation. These findings establish how the BCR-mTOR signaling axis regulates mucosal B cell responses after influenza infection.
Anupam et al. (Fri,) studied this question.