Full Activation of Autoreactive B Cells Requires Helper Signals from Plasmacytoid Dendritic Cells (99.32)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.99-99.32
• Main Authors: ding, chuanlin, Yan, Jun
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.99.32

Systemic lupus erythematosus (SLE) is characterized by dysregulated autoreactive B cell activation. Previous studies demonstrate that plasmacytoid dendritic cells (pDCs) play a pivotal role in the pathogenesis of SLE. This study was undertaken to investigate the mechanisms of interactions between pDCs and autoreactive B cells. After co-culture of anti-small nuclear ribonucleoprotein particle (snRNP) B cells with activated pDCs via toll-like receptor (TLR)-7 or -9 agonist, we found that pDCs could significantly enhance autoreactive B cell proliferation and autoantibody production. In addition, autoreactive B cell activation via BCR engagement was also augmented by activated pDCs. This in vitro enhancement effect was further demonstrated by an in vivo B cell adoptive transfer experiment, demonstrating that autoreactive B cell proliferation was significantly decreased in MyD-88-deficient mice compared to that in wildtype mice. Neutralization of IFN-α and IL-6 could abrogate partially enhanced B cell activation via pDCs. Transwell studies demonstrated that pDCs could provide activation signal to B cells in a cell-to-cell contact manner. The involvement of the ICAM-LFA-1 pathway, but not the CD40L-CD40 pathway, was discovered to mainly contribute to this effect. These data suggest that pDCs regulate autoreactive B cell activation by soluble factors as well as cell-to-cell direct interactions. (This work was supported by an Arthritis Foundation Postdoctoral Fellowship)