TY - JOUR
T1 - Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells
AU - Radhakrishnan, Suresh
AU - Nguyen, Loc T.
AU - Ciric, Bogoljub
AU - Ure, Daren R.
AU - Zhou, Bin
AU - Tamada, Koji
AU - Dong, Haidong
AU - Tseng, Su Yi
AU - Shin, Tahiro
AU - Pardoll, Drew M.
AU - Chen, Lieping
AU - Kyle, Robert A.
AU - Rodriguez, Moses
AU - Pease, Larry R.
PY - 2003/2/15
Y1 - 2003/2/15
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.170.4.1830
DO - 10.4049/jimmunol.170.4.1830
M3 - Article
C2 - 12574348
AN - SCOPUS:0037442244
SN - 0022-1767
VL - 170
SP - 1830
EP - 1838
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -