Loss of IFN-gamma 3’untranslated region AU-rich element affects B220+ B cell and plasmacytoid dendritic cell populations in novel murine lupus model (161.3)

• Published in: The Journal of immunology (1950) Vol. 188; no. 1_Supplement; pp. 161 - 161.3
• Main Authors: Hodge, Deborah, Berthet, Cyril, Coppola, Vincenzo, Shirota, Hidekazu, Reynolds, Della, Klinman, Dennis, Young, Howard
• Format: Journal Article
• Language: English
• Published: 01.05.2012
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.161.3

Interferon-gamma (IFN-g) is a key player in immunoregulation, inflammation and autoimmunity. We created a mouse with a162 nt deletion of an AU-rich element (ARE) region in the 3’UTR of the IFN-g gene. The ARE-deleted (ARE-Del) mice have chronic circulating serum IFN-g levels and develop a lupus-like disease characterized by DNA and nuclear antigen-specific autoantibodies and glomerulonephritis. B220+ B cells and plasmacytoid dendritic cells (pDCs) play a prominent role in systemic lupus erythematosus (SLE). We find alterations in both cell types. Greater B cell percentages are found in lymph nodes and thymus with a concomitant reduction in spleen. The B cells have an activated phenotype with increased CD69 and/or CD86 expression. The ARE-Del thymic B cell population is partially composed of B1a and B1b B cells and is correlated with increased thymic mRNA expression of the B cell chemoattractant, CXCL13. Splenic B cells down-regulate CD23 and CD21 with no change in surface markers CD19, B220, IgM, and IgD. The percentage of CD11c+, pDCA1+, B220+ Siglec H+ pDCs is increased in bone marrow and spleens from AU-deleted mice. Current studies are underway to further characterize the pDC population and to investigate expression of bone marrow-specific factors important for pDC development. Overall, these data demonstrate that low chronic IFN-g levels are sufficient to alter the phenotype and potentially the development of cells important for SLE disease onset and progression.