{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:58:36Z","timestamp":1781510316351,"version":"3.54.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Studies of mouse lupus models have linked the MHC H2b haplotype with the earlier appearance of antinuclear autoantibodies and the worsening of nephritis. However, it is unknown whether H2b by itself, in the context of pure nonlupus strains, is \u201csilent\u201d or sufficient with regard to loss of tolerance to chromatin (nucleosomes). In this study we show that, beginning \u223c6\u20139 mo of age, H2b-congenic BALB\/c (denoted BALB.B) mice, unlike BALB\/c (H2d) and H2k-congenic BALB\/c (denoted BALB.K) mice, develop strikingly increased serum levels of anti-chromatin Ab dominated by the IgG2a subclass, along with minor increase of Abs to DNA and moderately increased total serum IgG2a. The BALB.B mice did not have glomerulonephritis or an increased mortality rate. H2b-congenic C3H\/He mice (designated C3.SW mice), unlike C3H\/He (H2k) mice, showed low but measurable serum levels of chromatin-reactive IgG2a Abs and minor but significant hypergammaglobulinemia. By immunofluorescence, IgG2a of sera from both H2b-congenic strains stained HEp-2 cell nuclei, confirming the presence of antinuclear autoantibodies. Thus, in the context of two pure nonlupus genomes, the MHC H2b haplotype in homozygous form is sufficient to induce loss of tolerance to chromatin.<\/jats:p>","DOI":"10.4049\/jimmunol.0900579","type":"journal-article","created":{"date-parts":[[2009,8,5]],"date-time":"2009-08-05T21:46:31Z","timestamp":1249508791000},"page":"3542-3550","source":"Crossref","is-referenced-by-count":12,"title":["The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies"],"prefix":"10.1093","volume":"183","author":[{"given":"Kristian","family":"Hannestad","sequence":"first","affiliation":[{"name":"Institute of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Scott","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Oslo and Rikshospitalet University Hospital , Oslo,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,9,1]]},"reference":[{"key":"2026012811271896500_R1","first-page":"1687","article-title":"Genesis and evolution of anti-chromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen.","volume-title":"J. Clin. Invest.","year":"1993"},{"key":"2026012811271896500_R2","first-page":"1684","article-title":"Nucleosome-restricted antibodies are detected before anti-dsDNA and\/or antihistone antibodies in serum of MRL-Mp lpr\/lpr and +\/+ mice, and are present in kidney eluates of lupus mice with proteinuria.","volume-title":"Arthritis Rheum.","year":"1994"},{"key":"2026012811271896500_R3","first-page":"269","article-title":"Murine models of systemic lupus erythematosus.","volume-title":"Adv. Immunol.","year":"1985"},{"key":"2026012811271896500_R4","first-page":"419","article-title":"Immunologically active autoantigens: the role of Toll-like receptors in the development of chronic inflammatory disease.","volume-title":"Annu. Rev. Immunol.","year":"2007"},{"key":"2026012811271896500_R5","first-page":"1","article-title":"Systemic lupus erythematosus: multiple immunological phenotypes in a complex genetic disease.","volume-title":"Adv. Immunol.","year":"2006"},{"key":"2026012811271896500_R6","first-page":"83","article-title":"Genetics of SLE in mice.","volume-title":"Springer Semin. Immunopathol.","year":"2006"},{"key":"2026012811271896500_R7","first-page":"769","article-title":"Association of extensive polymorphisms in the SLAM\/CD2 gene cluster with murine lupus.","volume-title":"Immunity","year":"2004"},{"key":"2026012811271896500_R8","first-page":"1665","article-title":"Regulation of B cell tolerance by the lupus susceptibility gene Ly108.","volume-title":"Science","year":"2006"},{"key":"2026012811271896500_R9","first-page":"261","article-title":"Genetic susceptibility to systemic lupus erythematosus.","volume-title":"Annu. Rev. Immunol.","year":"1998"},{"key":"2026012811271896500_R10","first-page":"447","article-title":"Lessons from BXSB and related mouse models.","volume-title":"Int. Rev. Immunol.","year":"2000"},{"key":"2026012811271896500_R11","first-page":"794","article-title":"Genetics of human systemic lupus erythematosus: the emerging picture.","volume-title":"Curr. Opin. Immunol.","year":"2004"},{"key":"2026012811271896500_R12","first-page":"1062","article-title":"Epistatic suppression of systemic lupus erythematosus: fine mapping of Sles1 to less than 1 mb.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012811271896500_R13","first-page":"2761","article-title":"Antigen nonspecific effect of major histocompatibility complex haplotype on autoantibody levels in systemic lupus erythematosus-prone lpr mice.","volume-title":"J. Clin. Invest.","year":"1993"},{"key":"2026012811271896500_R14","first-page":"14654","article-title":"Role of the major histocompatibility complex class II Ea gene in lupus susceptibility in mice.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026012811271896500_R15","first-page":"295","article-title":"H-2-linked control of the Yaa gene-induced acceleration of lupus-like autoimmune disease in BXSB mice.","volume-title":"Eur. J. Immunol.","year":"1992"},{"key":"2026012811271896500_R16","first-page":"1189","article-title":"Prevention of systemic lupus erythematosus in autoimmune BXSB mice by a transgene encoding I-E \u03b1 chain.","volume-title":"J. Exp. Med.","year":"1993"},{"key":"2026012811271896500_R17","first-page":"94","article-title":"The Bm12 mutation and autoantibodies to Dsdna in Nzb.H-2Bm12 mice.","volume-title":"J. Immunol.","year":"1990"},{"key":"2026012811271896500_R18","first-page":"273","article-title":"Several mechanisms can account for defective E\u03b1 gene expression in different mouse haplotypes.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1983"},{"key":"2026012811271896500_R19","first-page":"660","article-title":"On the complexity of self.","volume-title":"Nature","year":"1991"},{"key":"2026012811271896500_R20","first-page":"307","article-title":"Prevention of murine lupus by an I-E \u03b1 chain transgene: protective role of I-E \u03b1 chain-derived peptides with a high affinity to I-Ab molecules.","volume-title":"Eur. J. Immunol.","year":"1996"},{"key":"2026012811271896500_R21","first-page":"787","article-title":"New insights into disease pathogenesis from mouse lupus genetics.","volume-title":"Curr. Opin. Immunol.","year":"2004"},{"key":"2026012811271896500_R22","first-page":"4620","article-title":"MHC class II molecules control murine B cell responsiveness to lipopolysaccharide stimulation.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012811271896500_R23","first-page":"451","article-title":"Use of selectively trypsinized nucleosome core particles to analyze the role of the histone \u201ctails\u201d in the stabilization of the nucleosome.","volume-title":"J. Mol. Biol.","year":"1989"},{"key":"2026012811271896500_R24","first-page":"1362","article-title":"Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A\/H2B\/DNA subnucleosomes.","volume-title":"J. Clin. Invest.","year":"1998"},{"key":"2026012811271896500_R25","first-page":"63","article-title":"\u03b3M rheumatoid factors reacting with nitrophenyl groups and denatured DNA.","volume-title":"Ann. NY Acad. Sci.","year":"1969"},{"key":"2026012811271896500_R26","first-page":"1374","article-title":"Predominant autoantibody production by early human B cell precursors.","volume-title":"Science","year":"2003"},{"key":"2026012811271896500_R27","first-page":"135","article-title":"A novel locus affecting serum levels of IgG2a maps to the murine H2 region.","volume-title":"Eur. J. Immunogenet.","year":"2000"},{"key":"2026012811271896500_R28","first-page":"2343","article-title":"Use of a novel elution regimen reveals the dominance of polyreactive antinuclear autoantibodies in lupus kidneys.","volume-title":"Arthritis Rheum.","year":"2003"},{"key":"2026012811271896500_R29","first-page":"121","article-title":"Antinucleosome autoantibodies bind directly to cell lines in vitro and via the Fc\u03b3RIIB receptor to B lymphocytes in vivo: a role for immune complexes in interactions between antinucleosome IgG2a and B cells of BXSB lupus mice.","volume-title":"Scand. J. Immunol.","year":"2004"},{"key":"2026012811271896500_R30","first-page":"381","article-title":"Pathogenic profiles and molecular signatures of antinuclear autoantibodies rescued from NZM2410 lupus mice.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012811271896500_R31","first-page":"205","article-title":"Quantitation and IgG subclass distribution of anti-chromatin autoantibodies in SLE mice.","volume-title":"Clin. Immunol. Immunopathol.","year":"1988"},{"key":"2026012811271896500_R32","first-page":"1271","article-title":"Isotypes of spontaneous and mitogen-induced autoantibodies in SLE-prone mice.","volume-title":"J. Immunol.","year":"1984"},{"key":"2026012811271896500_R33","first-page":"255","article-title":"Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells.","volume-title":"Nature","year":"1988"},{"key":"2026012811271896500_R34","first-page":"944","article-title":"Interferon-\u03b3 and B cell stimulatory factor-1 reciprocally regulate Ig isotype production.","volume-title":"Science","year":"1987"},{"key":"2026012811271896500_R35","first-page":"1022","article-title":"IFN-\u03b3 regulates the isotypes of Ig secreted during in vivo humoral immune responses.","volume-title":"J. Immunol.","year":"1988"},{"key":"2026012811271896500_R36","first-page":"687","article-title":"CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells.","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026012811271896500_R37","first-page":"1483","article-title":"CpG DNA redirects class-switching towards \u201cTh1-like\u201d Ig isotype production via TLR9 and MyD88.","volume-title":"Eur. J. Immunol.","year":"2004"},{"key":"2026012811271896500_R38","first-page":"740","article-title":"A Toll-like receptor recognizes bacterial DNA.","volume-title":"Nature","year":"2000"},{"key":"2026012811271896500_R39","first-page":"553","article-title":"TLR9\/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE.","volume-title":"J. Exp. Med.","year":"2006"},{"key":"2026012811271896500_R40","first-page":"2415","article-title":"TLR9 signaling in B cells determines class switch recombination to IgG2a.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012811271896500_R41","first-page":"1685","article-title":"Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies.","volume-title":"J. Clin. Invest.","year":"1999"},{"key":"2026012811271896500_R42","first-page":"1787","article-title":"The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026012811271896500_R43","first-page":"2352","article-title":"Genetic dissection of spontaneous autoimmunity driven by 129-derived chromosome 1 loci when expressed on C57BL\/6 mice.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012811271896500_R44","first-page":"277","article-title":"Spontaneous autoimmune disease in Fc\u03b3RIIB-deficient mice results from strain-specific epistasis.","volume-title":"Immunity","year":"2000"},{"key":"2026012811271896500_R45","first-page":"1167","article-title":"Genetic modifiers of systemic lupus erythematosus in Fc\u03b3RIIB\u2212\/\u2212 mice.","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2026012811271896500_R46","first-page":"E243","article-title":"Spontaneous autoimmunity in 129 and C57BL\/6 mice\u2013implications for autoimmunity described in gene-targeted mice.","volume-title":"PLoS Biol.","year":"2004"},{"key":"2026012811271896500_R47","first-page":"4724","article-title":"A critical role for Fc\u03b3RIIB in the induction of rheumatoid factors.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811271896500_R48","first-page":"489","article-title":"B cells acquire antigen from target cells after synapse formation.","volume-title":"Nature","year":"2001"},{"key":"2026012811271896500_R49","first-page":"6129","article-title":"Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012811271896500_R50","first-page":"503","article-title":"Cell surface recycling of internalized antigen permits dendritic cell priming of B cells.","volume-title":"Immunity","year":"2005"},{"key":"2026012811271896500_R51","first-page":"3482","article-title":"T-independent antibody responses to T-dependent antigens: a novel follicular dendritic cell-dependent activity.","volume-title":"J. Immunol.","year":"2009"},{"key":"2026012811271896500_R52","first-page":"3807","article-title":"A lupus-suppressor BALB\/c locus restricts IgG2 autoantibodies without altering intrinsic B cell-tolerance mechanisms.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012811271896500_R53","first-page":"237","article-title":"T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex.","volume-title":"Annu. Rev. Immunol.","year":"1985"},{"key":"2026012811271896500_R54","first-page":"329","article-title":"CD4+ T cells from lupus-prone mice are hyperresponsive to T cell receptor engagement with low and high affinity peptide antigens: a model to explain spontaneous T cell activation in lupus.","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026012811271896500_R55","first-page":"2842","article-title":"Epitope-dependent inhibition of T cell activation by the Ea transgene: an explanation for transgene-mediated protection from murine lupus.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811271896500_R56","first-page":"7770","article-title":"T cell-independent spontaneous loss of tolerance by anti-double-stranded DNA B cells in C57BL\/6 mice.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012811271896500_R57","first-page":"2227","article-title":"Dichotomous effects of complete versus partial class II major histocompatibility complex deficiency on circulating autoantibody levels in autoimmune-prone mice.","volume-title":"Arthritis Rheum.","year":"2004"},{"key":"2026012811271896500_R58","first-page":"2694","article-title":"The major murine systemic lupus erythematosus susceptibility locus Sle1 results in abnormal functions of both B and T cells.","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012811271896500_R59","first-page":"1349","article-title":"Role of TLR9 in anti-nucleosome and anti-DNA antibody Production in lpr mutation-induced murine lupus.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012811271896500_R60","first-page":"321","article-title":"Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012811271896500_R61","first-page":"417","article-title":"Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus.","volume-title":"Immunity","year":"2006"},{"key":"2026012811271896500_R62","first-page":"177","article-title":"Genetic control of antinuclear antibodies in mice inoculated with the Moloney leukaemia virus.","volume-title":"J. Immunogenet.","year":"1981"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/5\/3542\/62696753\/9605.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/5\/3542\/62696753\/9605.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:30:13Z","timestamp":1769617813000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/183\/5\/3542\/8053645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,1]]},"references-count":62,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2009,9,1]]},"published-print":{"date-parts":[[2009,9,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0900579","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,9]]},"published":{"date-parts":[[2009,9,1]]}}}