B cells in the pneumococcus-infected lung are heterogeneous and require CD4 + T cell help including CD40L to become resident memory B cells.

Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal protection in mice requires re-exposure to pneumococcus within days of initial infection. Serial surface marker phenotyping of B cell populations in a model of pneumococcal heterotypic immunity revealed that bacterial re-exposure stimulates the immediate accumulation of dynamic and heterogeneous populations of B cells in the lung, and is essential for the establishment of lung resident memory B (B _RM ) cells. The B cells in the early wave were activated, proliferating locally, and associated with both CD4 ⁺ T cells and CXCL13. Antagonist- and antibody-mediated interventions were implemented during this early timeframe to demonstrate that lymphocyte recirculation, CD4 ⁺ cells, and CD40 ligand (CD40L) signaling were all needed for lung B _RM cell establishment, whereas CXCL13 signaling was not. While most prominent as aggregates in the loose connective tissue of bronchovascular bundles, morphometry and live lung imaging analyses showed that lung B _RM cells were equally numerous as single cells dispersed throughout the alveolar septae. We propose that CD40L signaling from antigen-stimulated CD4 ⁺ T cells in the infected lung is critical to establishment of local B _RM cells, which subsequently protect the airways and parenchyma against future potential infections.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Etesami, Barker, Shenoy, De Ana, Arafa, Grifno, Matschulat, Vannini, Pihl, Breen, Soucy, Goltry, Ha, Betsuyaku, Browning, Varelas, Traber, Jones, Quinton, Maglione, Nia, Belkina and Mizgerd.)