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Spontaneous B cell hyperactivity in autoimmune-prone MRL mice

Nijnik, A; Ferry, H; Lewis, G; Rapsomaniki, E; Leung, JCH; Daser, A; Lambe, T; ... Cornall, RJ; + view all (2006) Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. INT IMMUNOL , 18 (7) 1127 - 1137. 10.1093/intimm/dxl047.

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Abstract

The MRL-lpr/lpr mouse strain is a commonly used model of the human autoimmune disease systemic lupus erythematosus (SLE). Although much is known about the contribution of the lpr Fas mutation to B cell tolerance breakdown, the role of the genetic background of the MRL strain itself is less well explored. In this study, we use the MD4 anti-hen egg lysozyme Ig (Ig(HEL)) transgenic system to explore B cell function in MRL+/+ and non-autoimmune mice. We demonstrate that MRL Ig(HEL) B cells show spontaneous hyperactivity in the absence of self-antigen, which is associated with low total B cell numbers but an expansion of the marginal zone B cell population. However, B cell anergy is normal in the presence of soluble lysozyme [soluble hen egg lysozyme (sHEL)], and MRL Ig(HEL) B cells undergo normal elimination in the presence of sHEL when competing with a polyclonal C57BL/6 B cell repertoire. We conclude that B cell hyperactivity may contribute to the autoimmune phenotype of MRL+/+ and MRL-lpr/lpr strains when it initiates antibody responses to rare or sequestered antigens that are below the threshold for tolerance induction, but that there is no B cell intrinsic defect in anergy in MRL mice.

Type: Article
Title: Spontaneous B cell hyperactivity in autoimmune-prone MRL mice
DOI: 10.1093/intimm/dxl047
Keywords: B lymphocytes, systemic lupus erythematosus (SLE), tolerance, SYSTEMIC-LUPUS-ERYTHEMATOSUS, SPLENIC MARGINAL ZONE, CD4(+) T-CELLS, BEARING AUTOANTIBODY TRANSGENES, REACTIVE LYMPHOCYTES-B, FAMILY-MEMBER BIM, NEW-ZEALAND BLACK, LPR MICE, FOLLICULAR EXCLUSION, DEVELOPMENTAL ARREST
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: http://discovery.ucl.ac.uk/id/eprint/1317150
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