Submitted July 6, 2007
Accepted March 3, 2008
IgG regulates the CD1 expression profile and lipid antigen presenting function in human dendritic cells via Fc
RIIa
Anna Smed-Sorensen*, Markus Moll, Tan-Yun Cheng, Karin Lore, Anna-Carin Norlin, Leif Perbeck, D. Branch Moody, Anna-Lena Spetz, and Johan K. Sandberg
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hopsital, Harvard Medical School, Boston, MA, United States
Department of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden
Department of Surgery, Karolinska University Hospital Solna, Stockholm, Sweden
* Corresponding author; email: smed-sorensen.anna{at}gene.com.
Dendritic cells (DCs) process and present bacterial and endogenous lipid antigens in complex with CD1 molecules to T cells and invariant NKT cells. However, different types of DCs, such as blood myeloid DCs and skin Langerhans cells exhibit distinct patterns of CD1a, CD1b, CD1c and CD1d expression. The regulation of such differences is incompletely understood. Here, we initially observed that monocyte-derived DCs cultured in an immunoglobulin-rich milieu expressed CD1d but not CD1a, CD1b and CD1c, whereas DCs cultured in the presence of low levels of immunoglobulins had an opposite CD1 profile. Based on this, we tested the possibility that immunoglobulins play a central role in determining these differences in DCs developing from monocytes. IgG-depletion and IVIg add-in experiments strongly supported a role for IgG in directing the CD1 expression profile. Blocking experiments indicated that this effect was mediated by Fc
RIIa (CD32a), and quantitative PCR data demonstrated that regulation of the CD1 profile occurred at the gene expression level. Finally, the ability of DCs to activate CD1-restricted NKT cells and T cells was determined by this regulatory effect of IgG. Our data strongly support an important role for IgG and FcRIIa in regulating the CD1 antigen presentation machinery of human DCs.
