Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells

Suresh Radhakrishnan, Loc T. Nguyen, Bogoljub Ciric, Daren R. Ure, Bin Zhou, Koji Tamada, Haidong M Dong, Su Yi Tseng, Tahiro Shin, Drew M. Pardoll, Lieping Chen, Robert A. Kyle, Moses Rodriguez, Larry R Pease

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Abstract

A human IgM Ab, serum-derived human IgM 12 (sHIgM12), is identified that binds mouse and human dendritic cells (DC), inducing dramatic immunopotentiation following treatment of the mouse DC in vitro. Competition, transfection, and knockout studies identified the ligand on mouse DC as the costimulatory molecule family member B7-DC. Potent T cell responses are stimulated by Ag-pulsed DC treated with the sHIgM12 Ab in vitro and upon adoptive transfer of Ab-treated Ag-pulsed DC into animals. The multivalent structure of pentameric IgM provides the potential for cross-linking cell surface targets, endowing the soluble Abs with biological potential not normally associated with immune function. The ability of the sHIgM12 Ab to potentiate the immune response is dependent on the multimeric structure of IgM, as bivalent monomers do not retain this property. Furthermore, pretreatment of DC with IgM monomers blocks subsequent potentiation by intact IgM pentamers, an indication that cross-linking of B7-DC on the cell surface is critical for potentiation of Ag presentation. These findings imply that, in addition to known costimulatory roles, B7-DC can function as a receptor for signals delivered by cells expressing B7-DC ligands.

Original languageEnglish (US)
Pages (from-to)1830-1838
Number of pages9
JournalJournal of Immunology
Volume170
Issue number4
StatePublished - Feb 15 2003

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Dendritic Cells
Immunoglobulin M
T-Lymphocytes
Antibodies
Serum
Ligands
Aptitude
Adoptive Transfer
Transfection

ASJC Scopus subject areas

  • Immunology

Cite this

Radhakrishnan, S., Nguyen, L. T., Ciric, B., Ure, D. R., Zhou, B., Tamada, K., ... Pease, L. R. (2003). Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells. Journal of Immunology, 170(4), 1830-1838.

Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells. / Radhakrishnan, Suresh; Nguyen, Loc T.; Ciric, Bogoljub; Ure, Daren R.; Zhou, Bin; Tamada, Koji; Dong, Haidong M; Tseng, Su Yi; Shin, Tahiro; Pardoll, Drew M.; Chen, Lieping; Kyle, Robert A.; Rodriguez, Moses; Pease, Larry R.

In: Journal of Immunology, Vol. 170, No. 4, 15.02.2003, p. 1830-1838.

Research output: Contribution to journalArticle

Radhakrishnan, S, Nguyen, LT, Ciric, B, Ure, DR, Zhou, B, Tamada, K, Dong, HM, Tseng, SY, Shin, T, Pardoll, DM, Chen, L, Kyle, RA, Rodriguez, M & Pease, LR 2003, 'Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells', Journal of Immunology, vol. 170, no. 4, pp. 1830-1838.
Radhakrishnan S, Nguyen LT, Ciric B, Ure DR, Zhou B, Tamada K et al. Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells. Journal of Immunology. 2003 Feb 15;170(4):1830-1838.
Radhakrishnan, Suresh ; Nguyen, Loc T. ; Ciric, Bogoljub ; Ure, Daren R. ; Zhou, Bin ; Tamada, Koji ; Dong, Haidong M ; Tseng, Su Yi ; Shin, Tahiro ; Pardoll, Drew M. ; Chen, Lieping ; Kyle, Robert A. ; Rodriguez, Moses ; Pease, Larry R. / Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells. In: Journal of Immunology. 2003 ; Vol. 170, No. 4. pp. 1830-1838.
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abstract = "A human IgM Ab, serum-derived human IgM 12 (sHIgM12), is identified that binds mouse and human dendritic cells (DC), inducing dramatic immunopotentiation following treatment of the mouse DC in vitro. Competition, transfection, and knockout studies identified the ligand on mouse DC as the costimulatory molecule family member B7-DC. Potent T cell responses are stimulated by Ag-pulsed DC treated with the sHIgM12 Ab in vitro and upon adoptive transfer of Ab-treated Ag-pulsed DC into animals. The multivalent structure of pentameric IgM provides the potential for cross-linking cell surface targets, endowing the soluble Abs with biological potential not normally associated with immune function. The ability of the sHIgM12 Ab to potentiate the immune response is dependent on the multimeric structure of IgM, as bivalent monomers do not retain this property. Furthermore, pretreatment of DC with IgM monomers blocks subsequent potentiation by intact IgM pentamers, an indication that cross-linking of B7-DC on the cell surface is critical for potentiation of Ag presentation. These findings imply that, in addition to known costimulatory roles, B7-DC can function as a receptor for signals delivered by cells expressing B7-DC ligands.",
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