AUTHOR=Etesami Neelou S. , Barker Kimberly A. , Shenoy Anukul T. , De Ana Carolina Lyon , Arafa Emad I. , Grifno Gabrielle N. , Matschulat Adeline M. , Vannini Michael E. , Pihl Riley M. F. , Breen Michael P. , Soucy Alicia M. , Goltry Wesley N. , Ha Catherine T. , Betsuyaku Hanae , Browning Jeffrey L. , Varelas Xaralabos , Traber Katrina E. , Jones Matthew R. , Quinton Lee J. , Maglione Paul J. , Nia Hadi T. , Belkina Anna C. , Mizgerd Joseph P. TITLE=B cells in the pneumococcus-infected lung are heterogeneous and require CD4+ T cell help including CD40L to become resident memory B cells JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1382638 DOI=10.3389/fimmu.2024.1382638 ISSN=1664-3224 ABSTRACT=

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 (BRM) 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 BRM 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 BRM 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 BRM cells, which subsequently protect the airways and parenchyma against future potential infections.