The Functional Response of B Cells to Antigenic Stimulation: A Preliminary Report of Latent Tuberculosis

• Published in: PloS one 2016-04, Vol.11 (4), p.e0152710-e0152710
• Main Authors: du Plessis, Willem J, Kleynhans, Léanie, du Plessis, Nelita, Stanley, Kim, Malherbe, Stephanus T, Maasdorp, Elizna, Ronacher, Katharina, Chegou, Novel N, Walzl, Gerhard, Loxton, Andre G
• Format: Article
• Language: English
• Subjects: Antigens; Antigens, Bacterial - immunology; B cells; B-Lymphocytes - immunology; Bacillus Calmette-Guerin vaccine; BCG; Biology and Life Sciences; Care and treatment; CD19 antigen; CD27 antigen; Cell interactions; Cells, Cultured; Cytokines; Cytokines - biosynthesis; Dosage and administration; Humans; Humoral immunity; Immunity; Immunologic Memory; Immunological memory; Inflammation; Inflammation Mediators - metabolism; Interleukin 10; Interleukin 17; Interleukin 21; Latent Tuberculosis - immunology; Lipopolysaccharides - pharmacology; Lymphocytes B; Medicine and Health Sciences; Memory cells; Mycobacterium tuberculosis; Pathogens; Regulators; Stimulation; T cell receptors; TLR4 protein; TLR9 protein; Toll-Like Receptor 9 - physiology; Toll-like receptors; Tuberculosis; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vaccine development; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152710

Mycobacterium tuberculosis (M.tb) remains a successful pathogen, causing tuberculosis disease numbers to constantly increase. Although great progress has been made in delineating the disease, the host-pathogen interaction is incompletely described. B cells have shown to function as both effectors and regulators of immunity via non-humoral methods in both innate and adaptive immune settings. Here we assessed specific B cell functional interaction following stimulation with a broad range of antigens within the LTBI milieu. Our results indicate that B cells readily produce pro- and anti-inflammatory cytokines (including IL-1β, IL-10, IL-17, IL-21 and TNF-α) in response to stimulation. TLR4 and TLR9 based stimulations achieved the greatest secreted cytokine-production response and BCG stimulation displayed a clear preference for inducing IL-1β production. We also show that the cytokines produced by B cells are implicated strongly in cell-mediated communication and that plasma (memory) B cells (CD19+CD27+CD138+) is the subset with the greatest contribution to cytokine production. Collectively our data provides insight into B cell responses, where they are implicated in and quantifies responses from specific B cell phenotypes. These findings warrant further functional B cell research with a focus on specific B cell phenotypes under conditions of active TB disease to further our knowledge about the contribution of various cell subsets which could have implications for future vaccine development or refined B cell orientated treatment in the health setting.