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The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae

Ercoli, G; Ramos-Sevillano, E; Nakajima, R; De Assis, RR; Jasinskas, A; Goldblatt, D; Felgner, P; ... Brown, J; + view all (2021) The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae. Frontiers in Immunology , 11 , Article 611661. 10.3389/fimmu.2020.611661. Green open access

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Abstract

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.

Type: Article
Title: The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2020.611661
Publisher version: https://doi.org/10.3389/fimmu.2020.611661
Language: English
Additional information: Copyright © 2021 Ercoli, Ramos-Sevillano, Nakajima, de Assis, Jasinskas, Goldblatt, Felgner, Weckbecker and Brown. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Streptococcus pneumoniae, anti-protein antibody, colonization, B cell depletion, CD20
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10120767
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