Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions Journal Article
| Authors: | Boruchov, A. M.; Heller, G.; Veri, M. C.; Bonvini, E.; Ravetch, J. V.; Young, J. W. |
| Article Title: | Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions |
| Abstract: | Human monocyte-derived DCs (moDCs) and circulating conventional DCs coexpress activating (CD32a) and inhibitory (CD32b) isoforms of IgG Fcγ receptor (FcγR) II (CD32). The balance between these divergent receptors establishes a threshold of DC activation and enables immune complexes to mediate opposing effects on DC maturation and function. IFN-γ most potently favors CD32a expression on immature DCs, whereas soluble antiinflammatory concentrations of monomeric IgG have the opposite effect. Ligation of CD32a leads to DC maturation, increased stimulation of allogeneic T cells, and enhanced secretion of inflammatory cytokines, with the exception of IL-12p70. Coligation of CD32b limits activation through CD32a and hence reduces the immunogenicity of moDCs even for a strong stimulus like alloantigen. Targeting CD32b alone does not mature or activate DCs but rather maintains an immature state. Coexpression of activating and inhibitory FcγRs by DCs reveals a homeostatic checkpoint for inducing tolerance or immunity by immune complexes. These findings have important implications for understanding the pathophysiology of immune complex diseases and for optimizing the efficacy of therapeutic mAbs. The data also suggest novel strategies for targeting antigens to the activating or inhibitory FcγRs on human DCs to generate either antigen-specific immunity or tolerance. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; pathophysiology; antigen expression; t-lymphocytes; mouse; cells, cultured; gene targeting; cell maturation; dendritic cell; animal experiment; inflammation; cell differentiation; monoclonal antibody; cytokine; immunological tolerance; lymphocyte activation; dendritic cells; gamma interferon; immunoglobulin g; antigen specificity; immunogenicity; fc receptor; receptors, igg; immunostimulation; antigens, cd; monocyte; monocytes; cytokine release; homeostasis; concentration (parameters); cell activation; alloantigen; isoantigens; t lymphocyte activation; interleukin 12; monomer; antigen antibody complex; interleukin-12; interferon type ii; antigen-antibody complex; dose-response relationship, immunologic; protein p70; cd32 antigen; cd32a antigen; cd32b antigen; immune complex disease; immune complex diseases |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 115 |
| Issue: | 10 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2005-10-01 |
| Start Page: | 2914 |
| End Page: | 2923 |
| Language: | English |
| DOI: | 10.1172/jci24772 |
| PUBMED: | 16167082 |
| PROVIDER: | scopus |
| PMCID: | PMC1201664 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 141" - "Export Date: 24 October 2012" - "CODEN: JCINA" - "Source: Scopus" |
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