Disintegration of lung B-cell follicles precedes increased inflammation and severe pathology in I/St mice hyper susceptible to tuberculosis.
Linge I.1, Tsareva A.1, 2, Kondratieva E.1, Apt A.1
1Central Research Institute for Tuberculosis, Moscow, Russia
2”Skoltech”, Moscow, Russia
The exact role of B cells in tuberculosis (TB) is still under consideration. It is well shown in TB patients and animal models that B cells infiltrate lungs and form B-cell follicles (BCFs) in close vicinity of granuloma. To clarify the involvement of lung BCFs in the progression of pathology or control of inflammation in this investigation we utilized two strains of mice with the opposite phenotype for TB infection, namely resistant C57BL/6(B6) and hyper susceptible I/St mice. Here we show different dynamics of BCF formation in susceptible and resistant strains of mice during the course of TB infection. The highest number of B cells and BCFs is detected in 8-10 weeks post aerosol infection (wpi) in both strains of mice. However, while a significant number of B cells and BCFs persist long in the chronic stage of infection (25-35 wpi) in the lung of B6 mice, in I/St mice BCFs are dissociated in 12-16wpi which is accompanied by severe pathology and formation of necrotic areas. At this time point (12wpi) the level of proinflammatory cytokines involved in the progression of pathology - IL1, IL-11, IL-17a, and TNF-α - is significantly increased in the lungs of I/St comparing to B6 mice. While the level of pro-survival receptor BAFFR is equal on lung B cells of both strains of mice, one possible explanation for quicker BCF dissociation is significantly increased FAS expression on lung B cells and their subsequent higher propensity to apoptosis in susceptible I/St mice. Thus, we suggest that disintegration of lung B-cell follicles contributes to uncontrolled inflammation in susceptible I/St mice and vice versa B cells and BCF in resistant B6 mice are associated with the containment of TB.