The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae
The anti-CD20 antibody Rituximab to deplete CD20+ B cells is an effective treatment for rheumatoid arthritis and B cell malignancies, but is associated with an increased incidence of respiratory infections. Using mouse models we have investigated the consequences of B cell depletion on natural and a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.611661/full |
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| author | Giuseppe Ercoli Elisa Ramos-Sevillano Rie Nakajima Rafael Ramiro de Assis Algis Jasinskas David Goldblatt Philip Felgner Gisbert Weckbecker Jeremy Brown |
| author_facet | Giuseppe Ercoli Elisa Ramos-Sevillano Rie Nakajima Rafael Ramiro de Assis Algis Jasinskas David Goldblatt Philip Felgner Gisbert Weckbecker Jeremy Brown |
| author_sort | Giuseppe Ercoli |
| collection | DOAJ |
| description | The anti-CD20 antibody Rituximab to deplete CD20+ B cells is an effective treatment for rheumatoid arthritis and B cell malignancies, but is associated with an increased incidence of respiratory infections. Using mouse models we have investigated the consequences of B cell depletion on natural and acquired humoral immunity to Streptococcus pneumoniae. B cell depletion of naïve C57Bl/6 mice reduced natural IgM recognition of S. pneumoniae, but did not increase susceptibility to S. pneumoniae pneumonia. ELISA and flow cytometry assays demonstrated significantly reduced IgG and IgM recognition of S. pneumoniae in sera from mice treated with B cell depletion prior to S. pneumoniae nasopharyngeal colonization compared to untreated mice. Colonization induced antibody responses to protein rather than capsular antigen, and when measured using a protein array B cell depletion prior to colonization reduced serum levels of IgG to several protein antigens. However, B cell depleted S. pneumoniae colonized mice were still partially protected against both lung infection and septicemia when challenged with S. pneumoniae after reconstitution of their B cells. These data indicate that although B cell depletion markedly impairs antibody recognition of S. pneumoniae in colonized mice, some protective immunity is maintained, perhaps mediated by cellular immunity. |
| first_indexed | 2024-12-15T00:17:26Z |
| format | Article |
| id | doaj.art-254598317059450e979cd18bc29cd6e8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-15T00:17:26Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-254598317059450e979cd18bc29cd6e82022-12-21T22:42:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.611661611661The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniaeGiuseppe Ercoli0Elisa Ramos-Sevillano1Rie Nakajima2Rafael Ramiro de Assis3Algis Jasinskas4David Goldblatt5Philip Felgner6Gisbert Weckbecker7Jeremy Brown8Centre for Inflammation and Tissue Repair, UCL Respiratory, Division of Medicine, University College Medical School, Rayne Institute, London, United KingdomCentre for Inflammation and Tissue Repair, UCL Respiratory, Division of Medicine, University College Medical School, Rayne Institute, London, United KingdomVaccine Research and Development Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, United StatesVaccine Research and Development Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, United StatesVaccine Research and Development Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, United StatesDepartment of Immunobiology, UCL Great Ormond Street Institute of Child Health, NIHR Biomedical Research Centre, London, United KingdomVaccine Research and Development Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, United StatesNovartis Institute for BioMedical Research, Novartis, Basel, SwitzerlandCentre for Inflammation and Tissue Repair, UCL Respiratory, Division of Medicine, University College Medical School, Rayne Institute, London, United KingdomThe anti-CD20 antibody Rituximab to deplete CD20+ B cells is an effective treatment for rheumatoid arthritis and B cell malignancies, but is associated with an increased incidence of respiratory infections. Using mouse models we have investigated the consequences of B cell depletion on natural and acquired humoral immunity to Streptococcus pneumoniae. B cell depletion of naïve C57Bl/6 mice reduced natural IgM recognition of S. pneumoniae, but did not increase susceptibility to S. pneumoniae pneumonia. ELISA and flow cytometry assays demonstrated significantly reduced IgG and IgM recognition of S. pneumoniae in sera from mice treated with B cell depletion prior to S. pneumoniae nasopharyngeal colonization compared to untreated mice. Colonization induced antibody responses to protein rather than capsular antigen, and when measured using a protein array B cell depletion prior to colonization reduced serum levels of IgG to several protein antigens. However, B cell depleted S. pneumoniae colonized mice were still partially protected against both lung infection and septicemia when challenged with S. pneumoniae after reconstitution of their B cells. These data indicate that although B cell depletion markedly impairs antibody recognition of S. pneumoniae in colonized mice, some protective immunity is maintained, perhaps mediated by cellular immunity.https://www.frontiersin.org/articles/10.3389/fimmu.2020.611661/fullStreptococcus pneumoniaeanti-protein antibodycolonizationB cell depletionCD20 |
| spellingShingle | Giuseppe Ercoli Elisa Ramos-Sevillano Rie Nakajima Rafael Ramiro de Assis Algis Jasinskas David Goldblatt Philip Felgner Gisbert Weckbecker Jeremy Brown The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae Frontiers in Immunology Streptococcus pneumoniae anti-protein antibody colonization B cell depletion CD20 |
| title | The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae |
| title_full | The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae |
| title_fullStr | The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae |
| title_full_unstemmed | The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae |
| title_short | The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae |
| title_sort | influence of b cell depletion therapy on naturally acquired immunity to streptococcus pneumoniae |
| topic | Streptococcus pneumoniae anti-protein antibody colonization B cell depletion CD20 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.611661/full |
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