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

Giuseppe Ercoli,Philip Felgner,Jeremy Brown,David Goldblatt,Elisa Ramos-Sevillano,Rie Nakajima,Rafael Ramiro De Assis,Algis Jasinskas,Gisbert Weckbecker

doi:10.3389/fimmu.2020.611661

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.

Highlights

B cells are a major component of the adaptive immunity, and are essential for the secretion of antibodies directed against “non-self” antigens
To mimic the effect of B cell depletion therapy, mice were injected with a mouse anti-CD20 Ab
Splenocytes from mice colonized with S. pneumoniae following IP administration of anti-CD20 antibody were analyzed 26 days after depletion and showed almost complete reconstitution of the B cell population (Figure 2A)

Summary

Introduction

B cells (of B lymphocytes) are a major component of the adaptive immunity, and are essential for the secretion of antibodies directed against “non-self” antigens. B Cell Depletion Immunity to S. pneumoniae diseases, and there are several B cell neoplastic conditions including lymphoma, chronic lymphocytic leukaemia and myeloma [4, 5]. Antibody-mediated B cell depletion therapies have been developed as effective treatments for multiple autoimmune diseases and B cell malignancies with an increasing range of clinical applications [6]. B cell depletion therapies are used to treat rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, immune thrombocytopenia, non-Hodgkin’s lymphoma or chronic lymphocytic leukaemia [10, 11]. A common complication of autoimmune and malignant disease are serious respiratory infections, which could be exacerbated by depleting the B cell repertoire by reducing levels of protective antibodies [12]. Despite the increased risk of respiratory infections, there are few data on how B cell therapy affects the subsets of specific antibodies to respiratory pathogens

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Results

Conclusion