Circulating B-Lymphocytes as Potential Biomarkers of Tuberculosis Infection Activity

Abstract

Accurate biomarkers of Mycobacterium tuberculosis infection activity would significantly improve early diagnosis, treatment and management of M. tuberculosis infection. We hypothesised that circulating B-lymphocytes may be useful biomarkers of tuberculosis (TB) infection status in highly TB-endemic settings. Ex-vivo and in-vitro mycobacteria-specific B-cell ELISPOT assays were used to examine the plasmablast (PB) and memory B-cell (MBC) responses in the peripheral blood of adult, healthy, community controls (n = 151) and of active TB patients (n = 48) living in Uganda. Frequencies of mycobacteria-specific PBs were markedly higher in active TB patients compared to healthy controls, and, conversely, MBCs were markedly higher in the healthy controls compared to active TB patients. In addition, the community controls with evidence of latent TB infection had higher peripheral blood PB and MBC responses than those without evidence of TB infection. These data demonstrate that peripheral blood B-cell responses are differentially modulated during latent and active M. tuberculosis infection, and suggest that the PB to MBC ratio may be a useful biomarker of TB infection activity.

Mycobacterium tuberculosisinfection boosts B cell responses to unrelated pathogens

“…We used in-house in vitro and ex-vivo B cell ELISPOTS to determine the frequency of TT-specific plasmablasts and MBCs respectively in APTB cases and healthy donors following methods described by Sebina et al (36,37). Cryopreserved PBMCs were thawed, resuspended in RPMI (Gibco by Life Technologies) containing 10% (v/v) fetal bovine serum, 2 mM L-glutamine (both from Sigma-Aldrich, UK) and 1x penicillin-streptomycin (Invitrogen).…”

What Have We Learnt about BCG Vaccination in the Last 20 Years?

“…B-cell and antibody responses in the context of TB have not been studied to the extent of their T-cell counterparts due to what may turn out to be an under-appreciation of their importance. Recent evidence suggests a role for functionally distinct antibody responses in latent TB infection ( 73 , 74 ) and antibody and memory B-cell responses in BCG-vaccinated adults have been demonstrated ( 75 , 76 ) and may correlate with a reduced risk of TB disease in infants ( 77 , 78 ).…”

Thinking Outside the Box: Innate- and B Cell-Memory Responses as Novel Protective Mechanisms Against Tuberculosis

“…Some preliminary findings suggest that the proportion of distinct MBC subsets may predict the clinical status of Mtbinfected patients (Figure 2), arguing in favor of a role of B cell memory in TB (108,(115)(116)(117)(118)(119). For instance, MBC, plasmablasts, and PCs subsets are significantly enriched in the circulation of patients with active TB, and their proportions diminish after the conclusion of anti-TB treatment, suggesting that these B cells subsets undergo a contraction phase after antigen clearance (119).…”

“…Thus, the dual presence of MBCs and plasmablasts in the peripheral blood has been proposed as a marker of resolving active disease and LTBI. On the other hand, the presence of activated antigen-specific plasmablasts but not MBCs in the peripheral circulation may reflect the initial stages of active TB and the lack of both MBCs and plasmablasts in circulation may indicate uncontrolled infection (118). Particularly, non-switched IgD+ MBCs have been found reduced in distinct tissue compartments during advanced active TB (120,121).…”

“…Particularly, non-switched IgD+ MBCs have been found reduced in distinct tissue compartments during advanced active TB (120,121). Other studies have found that higher proportions of circulating MBCs but not plasmablasts in peripheral blood along with a prominent serum antibody-mediated memory response is indicative of a healthy condition after sterilizing immunity following Mtb infection (118). This coincides with the observation that healthy subjects who have resided in TBendemic areas have greater frequencies of peripheral blood MBCs and antibody-mediated responses compared to subjects from other world areas (122).…”