biostudies-literaturede Mattos Barbosa MGNIBIB NIH HHSNIAID NIH HHSNIH Office of the Director150483https://www.ebi.ac.uk/biostudies/studies/S-EPMC8492324biostudies-literatureUnknown6(17)Host genes define the severity of inflammation and immunity but specific loci doing so are unknown. Here we show that TNF receptor superfamily member 13B (TNFRSF13B) variants, which enhance defense against certain pathogens, also control immune-mediated injury of transplants, by regulating innate B cells' functions. Analysis of TNFRSF13B in human kidney transplant recipients revealed that 33% of those with antibody-mediated rejection (AMR) but fewer than 6% of those with stable graft function had TNFRSF13B missense mutations. To explore mechanisms underlying aggressive immune responses, we investigated alloimmunity and rejection in mice. Cardiac allografts in Tnfrsf13b-mutant mice underwent early and severe AMR. The dominance and precocity of AMR in Tnfrsf13b-deficient mice were not causedJCI insightTNFRSF13B genotypes control immune-mediated pathology by regulating the functions of innate B cells.PMC8492324EB 022033R56 AI123262AI122369R01 AI122369R01 EB022033R21 AI159219R01 AI151588R21 AI117561R01 AI139633AI 151588AI117561Liu HPlatt JLBarnes Jde Mattos Barbosa MGHuynh DFu BBram RJGeha RSCascalho MSamaniego MPrak ETLFarkash EAZhang YShikanov ALefferts ARfalseTNFRSF13B genotypes control immune-mediated pathology by regulating the functions of innate B cells.Host genes define the severity of inflammation and immunity but specific loci doing so are unknown. Here we show that TNF receptor superfamily member 13B (TNFRSF13B) variants, which enhance defense against certain pathogens, also control immune-mediated injury of transplants, by regulating innate B cells' functions. Analysis of TNFRSF13B in human kidney transplant recipients revealed that 33% of those with antibody-mediated rejection (AMR) but fewer than 6% of those with stable graft function had TNFRSF13B missense mutations. To explore mechanisms underlying aggressive immune responses, we investigated alloimmunity and rejection in mice. Cardiac allografts in Tnfrsf13b-mutant mice underwent early and severe AMR. The dominance and precocity of AMR in Tnfrsf13b-deficient mice were not caused2021-01-01T00:00:00Z2021 Sep2026-05-08T10:33:26.49Z2022-02-11T11:58:01.695ZS-EPMC84923243428381110.1172/jci.insight.150483