Regulation of pulmonary plasma cell responses during secondary infection with influenza virus.

MacLean, Andrew J; Bonifacio, Joao P P L; Oram, Sophia L; Mohsen, Mona O; Bachmann, Martin F; Arnon, Tal I (2024). Regulation of pulmonary plasma cell responses during secondary infection with influenza virus. The Journal of experimental medicine, 221(7) Rockefeller Univ. Press 10.1084/jem.20232014

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During secondary infection with influenza virus, plasma cells (PCs) develop within the lung, providing a local source of antibodies. However, the site and mechanisms that regulate this process are poorly defined. Here, we show that while circulating memory B cells entered the lung during rechallenge and were activated within inducible bronchus-associated lymphoid tissues (iBALTs), resident memory B (BRM) cells responded earlier, and their activation occurred in a different niche: directly near infected alveoli. This process required NK cells but was largely independent of CD4 and CD8 T cells. Innate stimuli induced by virus-like particles containing ssRNA triggered BRM cell differentiation in the absence of cognate antigen, suggesting a low threshold of activation. In contrast, expansion of PCs in iBALTs took longer to develop and was critically dependent on CD4 T cells. Our work demonstrates that spatially distinct mechanisms evolved to support pulmonary secondary PC responses, and it reveals a specialized function for BRM cells as guardians of the alveoli.

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