International Immunology Advance Access originally published online on May 30, 2006
International Immunology 2006 18(7):1127-1137; doi:10.1093/intimm/dxl047
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Spontaneous B cell hyperactivity in autoimmune-prone MRL mice
1 Henry Wellcome Building of Molecular Physiology, Oxford University, Roosevelt Drive, Oxford, OX3 7BN, UK
2 Australian Cancer Research Foundation Genetics Laboratory, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
Correspondence to: R. Cornall; E-mail: richard.cornall{at}ccmp.ox.ac.uk
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 (IgHEL) transgenic system to explore B cell function in MRL+/+ and non-autoimmune mice. We demonstrate that MRL IgHEL 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 IgHEL 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.
Keywords: B lymphocytes, systemic lupus erythematosus (SLE), tolerance
Transmitting editor: D. Tarlinton
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