1. Spontaneous B cell hyperactivity in autoimmune-prone MRL mice
- Author
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Janson C. H. Leung, Richard J. Cornall, Anastasia Nijnik, Helen Ferry, Teresa Lambe, Eleni Rapsomaniki, Angelika Daser, Graham Lewis, and Christopher C. Goodnow
- Subjects
Mice, Inbred MRL lpr ,Immunology ,Population ,Mice, Transgenic ,Lymphocyte Activation ,urologic and male genital diseases ,medicine.disease_cause ,Autoimmunity ,Mice ,Species Specificity ,immune system diseases ,Marginal zone B-cell ,medicine ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,fas Receptor ,skin and connective tissue diseases ,education ,B cell ,Autoimmune disease ,B-Lymphocytes ,education.field_of_study ,biology ,Clonal anergy ,General Medicine ,medicine.disease ,Tolerance induction ,medicine.anatomical_structure ,Antibody Formation ,biology.protein ,Antibody - 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 MRL1/1 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 MRL1/1 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.
- Published
- 2006
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