Induction of a gene expression program in dendritic cells with a cross-linking IgM antibody to the co-stimulatory molecule B7-DC.

Frank A. Blocki, Suresh Radhakrishnan, Virginia P. Van Keulen, Karin L. Heckman, Bogoljub Ciric, Charles L Howe, Moses Rodriguez, Eugene D Kwon, Larry R Pease

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

While bivalent antibodies can block ligand-receptor interactions, IgM pentamers efficiently cross-link cell surface targets and evoke physiological responses. We have described one such interaction between an IgM antibody (Ab) and the B7-DC costimulatory molecule expressed by dendritic cells that induces strong antitumor immunity and modulates pathogenic responses associated with allergic asthma. Progressive changes in gene expression in dendritic cells activated by an IgM B7-DC cross-linking Ab resulted in the increased expression in 350 genes and decreased expression of more than 200 genes over the course of 24 h following Ab treatment. In particular, up-regulation of the caspase inhibitor FLIP and the chemokine receptor CCR7, and the down-regulation of the CXCR4 receptor provide a mechanistic basis of Ab-induced survival and enhanced migration into draining lymph nodes. Increased expression of both cell surface and secreted molecules known to be mediators of the immunomodulatory properties of dendritic cells was detected at both the levels of RNA and protein expression. This analysis documents the ability of IgM Ab to activate a gene expression cascade leading to important biological changes in cellular function and provides mechanistic insight into the potent immunomodulatory properties attributed to this Ab.

Original languageEnglish (US)
Pages (from-to)2408-2410
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume20
Issue number13
DOIs
StatePublished - Nov 2006

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B7 Antigens
Gene expression
Dendritic Cells
Immunoglobulin M
Gene Expression
Antibodies
Genes
CXCR4 Receptors
Molecules
Caspase Inhibitors
Chemokine Receptors
Immunity
Up-Regulation
Down-Regulation
Asthma
Lymph Nodes
RNA
Ligands

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Induction of a gene expression program in dendritic cells with a cross-linking IgM antibody to the co-stimulatory molecule B7-DC. / Blocki, Frank A.; Radhakrishnan, Suresh; Van Keulen, Virginia P.; Heckman, Karin L.; Ciric, Bogoljub; Howe, Charles L; Rodriguez, Moses; Kwon, Eugene D; Pease, Larry R.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 20, No. 13, 11.2006, p. 2408-2410.

Research output: Contribution to journalArticle

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