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 Blood, 15 May 2008, Vol. 111, No. 10, pp. 5037-5046.
Prepublished online as a Blood First Edition Paper on March 12, 2008; DOI 10.1182/blood-2007-07-099549.

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IMMUNOBIOLOGY

IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via Fc{gamma}RIIa

Anna Smed-Sörensen1,*, Markus Moll1,*, Tan-Yun Cheng2, Karin Loré1, Anna-Carin Norlin3, Leif Perbeck4, D. Branch Moody2, Anna-Lena Spetz1, and Johan K. Sandberg1

1 Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 2 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 3 Department of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden; and 4 Department of Surgery, Karolinska University Hospital Solna, Stockholm, Sweden

Dendritic cells (DCs) process and present bacterial and endogenous lipid antigens in complex with CD1 molecules to T cells and invariant natural killer T (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. IgG depletion and intravenous immunoglobulin (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{gamma}RIIa (CD32a), and quantitative polymerase chain reaction 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 demonstrate an important role for Fc{gamma}RIIa in regulating the CD1 antigen presentation machinery of human DCs.


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