Back

Mucosal B cell memory selection integrates tissue-specific microbial cues via the IgA BCR

Holgado, M. P.; Origlio, S.; Bertoia, L.; Moussa, M.; Trivedi, A.; Fiore, F.; Zarubica, A.; Slack, E.; Linterman, M. A.; Cogne, M.; Gregoire, C.; GAYA, M.

2025-05-05 immunology
10.1101/2025.04.30.651421 bioRxiv
Show abstract

B cells engender plasma cells (PCs) and memory B cells (MBCs) to combat recurrent pathogens. While B cell receptor (BCR) affinity dictates fate decisions in clonally-restricted set-ups, the driving factors in more complex systems remain unknown. Here, we show that memory selection during mucosal infection is imprinted by inherent cues from barrier tissues: lungs skew selection towards MBCs while the gut favors PC entry, even in response to the same pathogen. This divergence is linked to differential BCR isotype usage across barrier tissues rather than to affinity. In the gut, the commensal-induced TGF-{beta}-rich milieu promotes B cell class-switching to IgA. Consequently, the IgA BCR bias selection towards PCs, a process that is counteracted by its cytosolic tail domain. Overall, mucosal B cell selection integrates tissue-specific cues by strongly relying on BCR isotype usage rather than affinity, with implications for nasal and oral vaccine development. One sentence summaryDivergent B cell memory strategies evolved in lung and gut mucosa to counteract recurrent pathogens.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.