Development of murine lupus involves the combined genetic contribution of the SLAM and FcγR intervals within the Nba2 autoimmune susceptibility locus

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dc.contributor.authorJørgensen, Trine N.
dc.contributor.authorAlfaro, Jennifer
dc.contributor.authorEnriquez, Hilda L.
dc.contributor.authorJiang, Chao
dc.contributor.authorLoo, William M.
dc.contributor.authorAtencio, Stephanie
dc.contributor.authorGubbels Bupp, Melanie R.
dc.contributor.authorMailloux, Christina M.
dc.contributor.authorMetzger, Troy
dc.contributor.authorFlannery, Shannon
dc.contributor.authorRozzo, Stephen J.
dc.contributor.authorKotzin, Brian L.
dc.contributor.authorRosemblatt, Mario*
dc.contributor.authorBono, María Rosa
dc.contributor.authorErickson, Loren D.
dc.date.accessioned2025-05-16T12:44:27Z
dc.date.available2025-05-16T12:44:27Z
dc.date.issued2025-01
dc.descriptionIndexación: Scopus
dc.description.abstractAutoantibodies are of central importance in the pathogenesis of Ab-mediated autoimmune disorders. The murine lupus susceptibility locus Nba2 on chromosome 1 and the syntenic human locus are associated with a loss of immune tolerance that leads to antinuclear Ab production. To identify gene intervals within Nba2 that control the development of autoantibody-producing B cells and to determine the cellular components through which Nba2 genes accomplish this, we generated congenic mice expressing various Nba2 intervals where genes for the FcγR, SLAM, and IFN-inducible families are encoded. Analysis of congenic strains demonstrated that the FcγR and SLAM intervals independently controlled the severity of autoantibody production and renal disease, yet are both required for lupus susceptibility. Deregulated homeostasis of terminally differentiated B cells was found to be controlled by the FcγR interval where FcγRIIb-mediated apoptosis of germinal center B cells and plasma cells was impaired. Increased numbers of activated plasmacytoid dendritic cells that were distinctly CD19+ and promoted plasma cell differentiation via the proinflammatory cytokines IL-10 and IFNα were linked to the SLAM interval. These findings suggest that SLAM and FcγR intervals act cooperatively to influence the clinical course of disease through supporting the differentiation and survival of autoantibody-producing cells. Copyright © 2010 by The American Association of Immunologists, Inc.
dc.description.accesoabiertoSí
dc.description.agradThis work is supported by grants from the Lupus Research Institute, Arthritis Foundation, and National Institutes of Health Grant AR052902 to L.D.E., National Institutes of Health Grant 5R01AR37070-19 to B.L.K., Fondecyt Grant 1060253 to M. R., and Fondecyt Grant 1060834 and PFB 16 (Chile) to M.R.B.
dc.description.urihttps://journals-aai-org.recursosbiblioteca.unab.cl/jimmunol/article/184/2/775/111858/Development-of-Murine-Lupus-Involves-the-Combined
dc.identifier.citationJournal of Immunology. Volume 184, Issue 2, Pages 775 - 786. 15 January 2010
dc.identifier.doi10.4049/jimmunol.0901322
dc.identifier.folioFondecyt Grant 1060253 to M. R.
dc.identifier.folioFondecyt Grant 1060834 and PFB 16 (Chile) to M.R.B.
dc.identifier.generoM
dc.identifier.issn1550-6606
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/64716
dc.language.isoen
dc.subjectAnimals
dc.subjectAntigens
dc.subjectMurine Lupus
dc.subjectApoptosis
dc.subjectAutoantibodies
dc.subjectKidney Diseases
dc.subjectGenetic Predisposition to Disease
dc.subjectLupus Erythematosus
dc.subjectSystemic; Mice
dc.subjectCongenic
dc.subjectPlasma Cells
dc.titleDevelopment of murine lupus involves the combined genetic contribution of the SLAM and FcγR intervals within the Nba2 autoimmune susceptibility locus
dc.typeArtículo
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