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

• Published in: Frontiers in immunology Vol. 15; p. 1382638
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 23.04.2024
• Subjects: adaptive immunity; Animals; B cells; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - immunology; CD40 Ligand - immunology; CD40 Ligand - metabolism; Chemokine CXCL13 - metabolism; Disease Models, Animal; Immunologic Memory; Immunology; Lung - immunology; Lung - microbiology; Lung - pathology; Lymphocyte Activation - immunology; Memory B Cells - immunology; Memory B Cells - metabolism; Mice; Mice, Inbred C57BL; mucosal immunity; Pneumococcal Infections - immunology; pneumonia; Signal Transduction; Streptococcus pneumoniae - immunology; lung immunology; B cells; pneumonia; adaptive immunity; mucosal immunity
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1382638

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