Mycobacterium tuberculosis infection is associated with increased B cell responses to unrelated pathogens

Simon G Kimuda,John G Raynes,Moses Egesa,Bernard S Bagaya,Ismail Sebina,Steven G Smith,Angela Nalwoga,Jonathan Levin,Stephen Cose,Alison M Elliott,Irene Andia-Biraro

doi:10.1038/s41598-020-71044-4

Abstract

Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. However, it is not known whether natural M.tb infection or whether vaccination with, Mycobacterium bovis BCG, has a similar effect. This study investigated the effects of M.tb infection and BCG vaccination on B cell responses to heterologous pathogen recall antigens. Antibodies against several bacterial and viral pathogens were quantified by ELISA in 68 uninfected controls, 62 individuals with latent TB infection (LTBI) and 107 active pulmonary TB (APTB) cases, and 24 recently BCG-vaccinated adolescents and naive controls. Antibody avidity was investigated using surface plasmon resonance and B cell ELISPOTs were used to measure plasmablast and memory B cell responses (MBC) in APTB cases and healthy donor controls. APTB was associated with higher levels of antibodies to respiratory syncytial virus and measles virus, compared to uninfected controls. BCG vaccination did not alter levels of antibodies against heterologous pathogens. Tetanus toxoid (TT)-specific antibody avidity was increased in APTB cases in comparison to uninfected individuals and the ratio of TT-specific plasmablasts to MBCs in the APTB cases was 7:1. M.tb infection is associated with increased antibody responses to heterologous pathogens in human subjects.

Highlights

Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro
active pulmonary TB (APTB) cases and individuals with latent TB infection (LTBI) were older than the uninfected individuals and there was a larger proportion of males in the APTB group in comparison to the other two groups
In order to explore the possibility that M.tb infection may be driving differentiation of memory B cell responses (MBC) specific to unrelated recall antigens into plasmablasts in our study participants, we examined the frequency of TTspecific MBCs and plasmablasts in 48 APTB cases and 115 healthy donors using B cell ELISPOT assays

Summary

Introduction

Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. Studies in the past have shown that purified protein derivative (PPD) from M.tb can stimulate secretion of antibodies against measles, rubella and herpes simplex viruses from human peripheral blood mononuclear cells (PBMCs) in vitro[10] This finding suggests that M.tb may be able to enhance antibody/B-cell memory responses generated from previous exposure to unrelated pathogen-derived antigens. Human MBCs are prone to activation by polyclonal stimulation; studies by Bernasconi et al.[11] have shown that stimulation of these cells by bacterial CpG (cytosine-phosphate-guanine) DNA or by T cell cytokines can lead to their proliferation and expansion into antibody-secreting cells This hypothesis has not been investigated in regard to Mycobacterium tuberculosis exposure. It is not known whether natural M.tb infection has the same non-specific stimulatory effect on antibody responses to recall antigens from heterologous pathogens. We do not know whether recent vaccination with the related species, M. bovis BCG has a similar effect on serological recall responses to unrelated antigens

Methods

Results

Conclusion