Tonsillar immunity over time, from immune resistance to immune regulation

Abstract Background. The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results. We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells than those from older ones. Finally, we demonstrated the growth of a B cell subset metabolically adapted to catabolize adenosine triphosphate (CD20+CD39+CD73+ cells), as patients get older. Conclusions. This paper shed light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the tonsils over time. They are indicative of a shift from an effector type of immune response early in life, to a regulatory role at later stages, when limiting the tissue damage gets critical. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites.