Phenotypic analysis of peripheral B cell populations during Mycobacterium tuberculosis infection and disease

Abstract

BackgroundMycobacterium tuberculosis (Mtb) remains an unresolved threat resulting in great annual loss of life. The role of B cells during the protective immunity to Mtb is still unclear. B cells have been described as effector cells in addition to their role as antibody producing cells during disease.Here we aim to identify and characterize the frequency of peripheral B-cell subpopulations during active Tuberculosis and over treatment response. Analysis were done for both class switched (CS) and non-class switched (NCS) phenotypes. Methods We recruited participants with active untreated pulmonary Tuberculosis, other lung diseases and healthy community controls. All groups were followed up for one week from recruitment and the TB cases till the end of treatment (month 6).ResultsPeripheral blood samples were collected, stained with monoclonal antibodies to CD19+ cells, Immunoglobulin (Ig) M, plasma cells (CD 138+), marker of memory (CD27+), immune activation (CD23+) and acquired on a flow cytometer. Circulating Marginal zone B cells (CD19+IgM+CD23−CD27+) and memory phenotypes are able to distinguish between TB diagnosis and end of treatment. The frequency of mature B cells from TB cases are lower than that of other-lung diseases at diagnosis. A subpopulation of activated memory B cells (CD19+IgM+CD23+CD27+) cells are present at the end of TB treatment.ConclusionsThis study identified distinctive B cell subpopulations present during active TB disease and other lung disease conditions. These cell populations warrants further examination in larger studies as it may be informative as cell markers or as effectors/regulators in TB disease or TB treatment response.

Both B‐1a and B‐1b cells exposed to Mycobacterium tuberculosis lipids differentiate into IgM antibody‐secreting cells

“…The details of B‐cell and IgM antibody dynamics during TB, anti‐TB therapy and vaccination in humans remain unclear. A recent study found distinct B‐cell subpopulations in peripheral blood during active TB disease and other lung disease conditions . Although Plessis et al .…”

Immunoglobulin profile and B-cell frequencies are altered with changes in the cellular micro-environment independent of the stimulation conditions

“…Current research findings have signified the importance of B-cells during M.tb infection, in which absence or impaired function of this immune cell type has been associated with poor disease prognosis (Achkar et al, 2015; Bénard et al, 2018; Du Plessis et al, 2016a, 2016b; Rao et al, 2015). For decades, the primary function of B-cells was considered to be antibody secretion, forming part of the adaptive humoral response (Abbas et al, 2014; Zabriskie, 2009).…”

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

“…Additionally, another study found that LLPCs are important contributors of cytokine production during LTBI (115). MBCs and LLPCs generate the AMIR through the production of IL-21 and the subsequent induction of a B cell maturation loop involving the formation of PCs (108,116). Preliminary evidence suggests that this response is crucial for controlling Mtb infection (108,116).…”

“…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).…”

“…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). Indeed, the maintenance of MBCs in circulation is dependent on the presence of Mtb antigens and can be eliminated after 12 weeks of antibiotic treatment (116), but serum IgG levels remain augmented even after a 6 month course of antibiotic therapy in TB patients (119). Thus, during active TB, the presence of the pathogen may trigger the generation of highaffinity antibody-mediated memory responses to Mtb antigens.…”