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

Abstract

Lung tissue–resident memory B (B_RM) cells are important in establishing protective immunity against respiratory pathogens. However, the pathways regulating the accumulation of lung B_RM 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 B_RM 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 B_RM cells during their development. Lung B_RM 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 B_RM cell accumulation. Conversely, inhibition of mTOR using rapamycin reduced NFATC1 and EGR2 expression and promoted lung B_RM cell accumulation. These findings establish how the BCR-mTOR signaling axis regulates mucosal B cell responses after influenza infection.