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• W2587272804 abstract "Systemic lupus erythematosus (SLE) is an autoimmune disease that reflects a failure to block the production of self-reactive antibodies, especially those that bind double-stranded DNA (dsDNA). Backcrossing the lupus-prone NZM2410 genome onto C57BL/6 led to the identification of three genomic intervals, termed sle1, sle2 and sle3, which are associated with lupus susceptibility. We previously generated a C57BL/6 strain congenic for an immunoglobulin DH locus (ΔD–iD) that enriches for arginine at dsDNA-binding positions. We individually introduced the ΔD–iD allele into the three sle strains to test whether one or more of these susceptibility loci could affect the developmental fate of B cells bearing arginine-enriched CDR-H3s, the CDR-H3 repertoire created by the DH and the prevalence of dsDNA-binding antibodies. We found that the combination of the ΔD–iD allele and the sle1 locus led to a decrease in mature, recirculating B cell numbers and an increase in marginal zone cell numbers while maintaining a highly charged CDR-H3 repertoire. ΔD–iD and sle2 had no effect on peripheral B cell numbers, but the CDR-H3 repertoire was partially normalized. ΔD–iD and sle3 led to an increase in marginal zone B cell numbers, with some normalization of hydrophobicity. Mice with ΔD–iD combined with either sle1 or sle3 had increased production of dsDNA-binding IgM and IgG by 12 months of age. These findings indicate that the peripheral CDR-H3 repertoire can be categorically manipulated by the effects of nonimmunoglobulin genes." @default.
• W2587272804 created "2017-02-17" @default.
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• W2587272804 date "2017-01-02" @default.
• W2587272804 modified "2023-10-16" @default.
• W2587272804 title "Alterations in B cell development, CDR-H3 repertoire and dsDNA-binding antibody production among C57BL/6 <i>ΔD−iD</i> mice congenic for the lupus susceptibility loci <i>sle1, sle2</i> or <i>sle3</i>" @default.
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• W2587272804 doi "https://doi.org/10.1080/08916934.2016.1272597" @default.
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