Michelle Linterman : Type I interferon remodels the lung to promote ectopic GC formation during influenza A virus infection

Key Speakers

Babraham Institute, Cambridge, UK


Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease and cancer. Despite their relative ubiquity, little is known about the mechanism(s) through which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here we show that type I interferon produced after pulmonary viral infection induces CXCL13 in lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal centre formation. This identifies type I IFN signaling as a novel inducer of CXCL13 and demonstrates that this cytokine can promote lung remodeling, converting a non-lymphoid tissue to one capable of supporting a highly ordered functional tertiary lymphoid structure.


When higher organisms are infected by pathogens the immune system responds with the coordinated activation of many different cell types, each with their own specific role to bring about pathogen clearance, and subsequently generate immunological memory. Within the adaptive immune system helper CD4+ T cells and B cells specific for the infectious organism are recruited to become activated effector cells and a proportion of these cells will go on to become memory cells that are able to respond quickly to future infections.

Germinal centres are sites within tissues such as the tonsils, spleen and lymph nodes where B cells proliferate and differentiate during a normal immune response to an infection. Because of the central role of the germinal centre in generating immunological memory, a potent germinal centre response is critical for a successful response to vaccination. With advancing age, the size of the germinal centre response and the efficacy of vaccination diminish, and T cells are one of the primary contributors to this decline.

Our research is focused on understanding the cellular and molecular changes that occur in T cells with age that contribute to the age-dependent decline in the germinal centre response.