02622nas a2200553   4500000000100000000000100001008004100002260001200043653002200055653002100077653002900098653001300127100001800140700002100158700002700179700001800206700002100224700002400245700001900269700002100288700001700309700001500326700002800341700001300369700002300382700002200405700002000427700002000447700001800467700001800485700001800503700001900521700002100540700001500561700001800576700002200594700002200616700001700638700002400655700001800679700001800697700001800715245006700733856005500800300001200855490000700867520118000874022001402054       2021                            d  c2021-0110aAdaptive immunity10aGerminal centres10aImmunological techniques10avaccines1 aLisa E. Wagar1 aAmeen Salahudeen1 aChristian M. Constantz1 aBen S. Wendel1 aMichael M. Lyons1 aVamsee Mallajosyula1 aLauren P. Jatt1 aJulia Z. Adamska1 aLisa K. Blum1 aNeha Gupta1 aKatherine J. L. Jackson1 aFan Yang1 aKatharina Röltgen1 aKrishna M. Roskin1 aKelly M. Blaine1 aKara D. Meister1 aIram N. Ahmad1 aMario Cortese1 aEmery G. Dora1 aSean N. Tucker1 aAnne I. Sperling1 aAarti Jain1 aD. Huw Davies1 aPhilip L. Felgner1 aGregory B. Hammer1 aPeter S. Kim1 aWilliam H. Robinson1 aScott D. Boyd1 aCalvin J. Kuo1 aMark M. Davis00aModeling human adaptive immune responses with tonsil organoids  uhttps://www.nature.com/articles/s41591-020-01145-0  a125-1350 v273 aMost of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.  a1546-170X