PMID- 16735376 OWN - NLM STAT- MEDLINE DCOM- 20060818 LR - 20171116 IS - 0953-8178 (Print) IS - 0953-8178 (Linking) VI - 18 IP - 7 DP - 2006 Jul TI - Spontaneous B cell hyperactivity in autoimmune-prone MRL mice. PG - 1127-37 AB - 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. FAU - Nijnik, Anastasia AU - Nijnik A AD - Henry Wellcome Building of Molecular Physiology, Oxford University, Roosevelt Drive, Oxford, OX3 7BN, UK. FAU - Ferry, Helen AU - Ferry H FAU - Lewis, Graham AU - Lewis G FAU - Rapsomaniki, Eleni AU - Rapsomaniki E FAU - Leung, Janson C H AU - Leung JC FAU - Daser, Angelika AU - Daser A FAU - Lambe, Teresa AU - Lambe T FAU - Goodnow, Christopher C AU - Goodnow CC FAU - Cornall, Richard J AU - Cornall RJ LA - eng GR - Wellcome Trust/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060530 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (fas Receptor) SB - IM MH - Animals MH - Antibody Formation/genetics/*immunology MH - B-Lymphocytes/*immunology/pathology MH - Humans MH - Lupus Erythematosus, Systemic/genetics/*immunology/pathology MH - Lymphocyte Activation/genetics/*immunology MH - Mice MH - Mice, Inbred MRL lpr MH - Mice, Transgenic MH - Species Specificity MH - fas Receptor/genetics/immunology EDAT- 2006/06/01 09:00 MHDA- 2006/08/19 09:00 CRDT- 2006/06/01 09:00 PHST- 2006/06/01 09:00 [pubmed] PHST- 2006/08/19 09:00 [medline] PHST- 2006/06/01 09:00 [entrez] AID - dxl047 [pii] AID - 10.1093/intimm/dxl047 [doi] PST - ppublish SO - Int Immunol. 2006 Jul;18(7):1127-37. doi: 10.1093/intimm/dxl047. Epub 2006 May 30.