Spontaneous B cell hyperactivity in autoimmune-prone MRL mice

• Published in: International immunology Vol. 18; no. 7; pp. 1127 - 1137
• Main Authors: Nijnik, Anastasia, Ferry, Helen, Lewis, Graham, Rapsomaniki, Eleni, Leung, Janson C. H., Daser, Angelika, Lambe, Teresa, Goodnow, Christopher C., Cornall, Richard J.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-07-2006; Oxford Publishing Limited (England)
• Subjects: Animals; Antibody Formation - genetics; Antibody Formation - immunology; B lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - pathology; fas Receptor - genetics; fas Receptor - immunology; Humans; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Mice, Inbred MRL lpr; Mice, Transgenic; Species Specificity; systemic lupus erythematosus (SLE); tolerance
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxl047

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.