tetano
Editor, Senior Moderator
Sci Immunol
. 2026 Mar 20;11(117):eadw1664.
doi: 10.1126/sciimmunol.adw1664. Epub 2026 Mar 20.
The B cell receptor-mTOR signaling axis restricts the accumulation of lung tissue-resident memory B cells after influenza infection
Kumari Anupam[SUP] 1 [/SUP], Komal Patel[SUP] 1 [/SUP], Pradhnesh Andhare[SUP] 1 [/SUP], Brittany Henry[SUP] 1 [/SUP], Christopher H Hanson[SUP] 1 [/SUP], Lizzette Pérez-Pérez[SUP] 1 [/SUP], Peggy L Kendall[SUP] 1 2 [/SUP], Brian J Laidlaw[SUP] 1 [/SUP]
Affiliations
Lung tissue-resident memory B (B[SUB]RM[/SUB]) cells are important in establishing protective immunity against respiratory pathogens. However, the pathways regulating the accumulation of lung B[SUB]RM[/SUB] 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[SUB]RM[/SUB] 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[SUB]RM[/SUB] cells during their development. Lung B[SUB]RM[/SUB] 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[SUB]RM[/SUB] cell accumulation. Conversely, inhibition of mTOR using rapamycin reduced NFATC1 and EGR2 expression and promoted lung B[SUB]RM[/SUB] cell accumulation. These findings establish how the BCR-mTOR signaling axis regulates mucosal B cell responses after influenza infection.
. 2026 Mar 20;11(117):eadw1664.
doi: 10.1126/sciimmunol.adw1664. Epub 2026 Mar 20.
The B cell receptor-mTOR signaling axis restricts the accumulation of lung tissue-resident memory B cells after influenza infection
Kumari Anupam[SUP] 1 [/SUP], Komal Patel[SUP] 1 [/SUP], Pradhnesh Andhare[SUP] 1 [/SUP], Brittany Henry[SUP] 1 [/SUP], Christopher H Hanson[SUP] 1 [/SUP], Lizzette Pérez-Pérez[SUP] 1 [/SUP], Peggy L Kendall[SUP] 1 2 [/SUP], Brian J Laidlaw[SUP] 1 [/SUP]
Affiliations
- PMID: 41860993
- DOI: 10.1126/sciimmunol.adw1664
Lung tissue-resident memory B (B[SUB]RM[/SUB]) cells are important in establishing protective immunity against respiratory pathogens. However, the pathways regulating the accumulation of lung B[SUB]RM[/SUB] 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[SUB]RM[/SUB] 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[SUB]RM[/SUB] cells during their development. Lung B[SUB]RM[/SUB] 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[SUB]RM[/SUB] cell accumulation. Conversely, inhibition of mTOR using rapamycin reduced NFATC1 and EGR2 expression and promoted lung B[SUB]RM[/SUB] cell accumulation. These findings establish how the BCR-mTOR signaling axis regulates mucosal B cell responses after influenza infection.