Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells Journal Article
| Authors: | Dhodapkar, K. M.; Kaufman, J. L.; Ehlers, M.; Banerjee, D. K.; Bonvini, E.; Koenig, S.; Steinman, R. M.; Ravetch, J. V.; Dhodapkar, M. V. |
| Article Title: | Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells |
| Abstract: | The final differentiation or maturation of dendritic cells (DCs) in response to environmental stimuli influences their ability to both initiate immunity and determine the quality of the response to antigens. Circulating immune complexes and cell-bound immunoglobulins present in normal human sera represent a potential stimulus for inadvertent DC activation in the steady state and during autoimmunity. Here, we show that selective blockade of the inhibitory Fcγ receptor (FcγR) FcγRIIb with recently developed monoclonal antibodies leads to maturation of human monocyte-derived DCs, which depends on the presence of IgG in normal human plasma. Plasma, in the presence of an FcγRIIb blockade, caused the DCs to up-regulate the expression of costimulatory molecules and to produce the inflammatory mediator IL-12p70. FcγRIIb blockade of DCs loaded with tumor cells led to increased tumor-specific T cell immunity without the need for exogenous stimuli other than human plasma. Therefore, the activation status of DCs in the presence of normal human serum depends on the balance between activating and inhibitory FcγRs and can be enhanced by new antibodies that react selectively with FcγRIIb. These data suggest an approach for modifying this balance to enhance immunity to immune complexes and antibody-coated tumor cells and to silence DC activation by immune complexes in autoimmune states. © 2005 by The National Academy of Sciences of the USA. |
| Keywords: | protein expression; unclassified drug; human cell; protein function; neoplasms; t-lymphocytes; cell maturation; dendritic cell; interleukin 12p70; cell differentiation; cell line, tumor; monoclonal antibody; dendritic cells; antibodies, monoclonal; immunoglobulin g; vaccination; tumor cell; tumor immunity; fc receptor; autoimmunity; receptors, igg; immunophenotyping; upregulation; protein subunits; monocytes; cell activation; autoantibodies; plasma; interleukin 12; myeloma; antigen antibody complex; cross presentation; myeloma cell; cross-presentation; interleukin-12; fc gamma receptor 2b |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 102 |
| Issue: | 8 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2005-02-22 |
| Start Page: | 2910 |
| End Page: | 2915 |
| Language: | English |
| DOI: | 10.1073/pnas.0500014102 |
| PUBMED: | 15703291 |
| PROVIDER: | scopus |
| PMCID: | PMC549508 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 117" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Source: Scopus" |
