LAUSR

Germinal centers (GC) are central places for the development of adaptive immune responses. While their development follows a first wave of extra-follicular activation, they uniquely contribute to the development of long-term responses including both diversified memory B cells with strong ability to activate and differentiate upon antigen re-challenge, and long-lived plasma cells producing highaffinity class-switched antibodies. They are central to protective immune responses against microbial or tumor-associated antigens, but they are also major sites where dealing with peripheral tolerance to autoantigens, programmed cell death and with the hazardous outcomes of DNA lesions inflicted to B-cells. There is currently no definitive model accounting for all the outcomes of GC formation, since these evolving structures integrate stimulating and inhibitory signals frommultiple origins, including antigens, chemokines, cytokines, specific antibody level and they dynamically evolve so that the very same factors initially promoting GC development can later contribute to GC resolution. In contexts of chronic local inflammation, “GC-like” tertiary lymphoid structures (TLS) have long been reported within some non-lymphoid tissues and they recently received strong attention for their contribution to tumor immunology. They share structural and functional characteristics with GC that form in the secondary lymphoid organs. TLS are induced by persistent infection, autoimmune disorders and cancer. Interestingly in many cancer types, a good correlation has been reported between richness in TLS in tumor site and prolonged patient survival (1, Trüb et al.). The cellular and molecular signals that govern the induction and the fate of TLS in such pathological situations are not well-understood, but are among the hotest research questions in this emerging TLS-Cancer topic with potential for new discovery in B cell focused immunotherapies. We therefore believe that classical GC and TLS structures are the two sides of the general mechanism of immune response and immune surveillance. In this Research Topic of Frontiers in Immunology, Kennedy and Clark from Chicago University, review the general compartments and connections at work in GCs. In a perspective paper notably commenting conflicting data about the role of hypoxia within the GC, Boothby et al. propose