Spontaneous B cell hyperactivity in autoimmune-prone MRL mice.
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.
Nijnik
Anastasia
A
Henry Wellcome Building of Molecular Physiology, Oxford University, Roosevelt Drive, Oxford, OX3 7BN, UK.
Ferry
Helen
H
Lewis
Graham
G
Rapsomaniki
Eleni
E
Leung
Janson C H
JC
Daser
Angelika
A
Lambe
Teresa
T
Goodnow
Christopher C
CC
Cornall
Richard J
RJ
D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D013045:Species Specificity; D019014:fas Receptor / Q000235:genetics / Q000276:immunology
D019014:fas Receptor