Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection

• Published in: Frontiers in immunology Vol. 13; p. 750068
• Main Authors: Linge, Irina, Tsareva, Anastasiya, Kondratieva, Elena, Dyatlov, Alexander, Hidalgo, Juan, Zvartsev, Ruslan, Apt, Alexander
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27.01.2022
• Subjects: Ablation Techniques; Adaptive Immunity; Animals; B-cells; B-Lymphocytes - immunology; Female; IL-6; Immunology; Interleukin-6 - analysis; Interleukin-6 - genetics; Interleukin-6 - immunology; lung inflammation; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; T cells; tuberculosis; Tuberculosis, Pulmonary - immunology; B-cells; T cells; IL-6; tuberculosis; lung inflammation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.750068

The role of B cells migrating to the lung and forming follicles during tuberculosis (TB) inflammation is still the subject of debate. In addition to their antibody production and antigen-presenting functions, B cells secrete different cytokines and chemokines, thus participating in complex networks of innate and adaptive immunity. Importantly, lung B-cells produce high amounts of the pleiotropic gp130 cytokine IL-6. Its role during TB infection remains controversial, partly due to the fact that IL-6 is produced by different cell types. To investigate the impact of IL-6 produced by B cells on TB susceptibility and immune responses, we established a mouse strain with specific IL-6 deficiency in B cells (CD19cre-IL-6fl/fl, B-IL-6KO) on the B6 genetic background. Selective abrogation of IL-6 in B cells resulted in shortening the lifespan of TB-infected B-IL-6KO mice compare to the wild-type controls. We provide evidence that at the initial TB stages B cells serve as a critical source of IL-6. In the lung, the effect of IL-6 deficiency in B cells is associated rather with B and T cell functioning, than with macrophage polarization. TB-infected B-IL-6KO mice displayed diminished sizes of B cells themselves, CD4 + IFN-γ + , Th17 + , and CD4 + CXCR5 + follicular T cell populations. The pleiotropic effect of B-cell-derived IL-6 on T-cells demonstrated in our study bridges two major lymphocyte populations and sheds some light on B- and T-cells interactions during the stage of anti-TB response when the host switches on a plethora of acquired immune reactions.