Deciphering molecular mechanisms controlling GC initiation has attracted the attention of immunologists in the last decade, aiming to understand the stepwise immune response and improve vaccination strategies. In this regard, every time is more evident that GC initiation entails critical metabolic changes in the immune cells. Thus, characterisation of the metabolic profile of each immune cell and understanding how metabolism instructs intrinsic cell activation, proliferation, and differentiation in the GC has become an essential field of study. However, GC is a double-edged sword: while a deficient GC initiation can lead to immunodeficiencies, an overactivation of GC can lead to GC-derived lymphomas or autoimmune diseases. Therefore, in addition to GC initiation, the processes leading to the GC reaction and termination of the cellular expansion are also of high scientific and clinical interest. However, the mechanisms for this GC shutdown have been disregarded until now, considering them as just a passive process.

Our laboratory has generated ground-breaking results showing that GC shutdown is actively triggered by a precise shift of the metabolic profile of GC B cells. Moreover, our data suggest that the metabolic activity of B lymphocytes not only impacts B cells themselves but instructs the metabolic rewiring and fate differentiation of neighbouring T lymphocytes. We hypothesise that massive proliferation at the GC must lead to changes in the substrate availability at the GC microenvironment. These changes may trigger a precise metabolic rewiring in B cells, establishing what we have named as a ¨shutdown metabolic profile¨. This metabolic profile leads to the production of particular signalling molecules, which will both shape B cell function intrinsically and will signal on neighbouring immune cells, driving, all together, the GC shutdown.

Our group aims to characterise the ¨shutdown metabolic profile¨, how it is triggered, and identify all the molecular entities that mediate it. The obtained information will be evaluated in terms of its therapeutic potential in B cell lymphomas and leukaemias, autoimmune diseases, and to improve, in the future, vaccination strategies.