Naturally occurring human IgM antibody that binds B7-DC and potentiates T cell stimulation by dendritic cells.
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.
Radhakrishnan
Suresh
S
Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Nguyen
Loc T
LT
Ciric
Bogoljub
B
Ure
Daren R
DR
Zhou
Bin
B
Tamada
Koji
K
Dong
Haidong
H
Tseng
Su-Yi
SY
Shin
Tahiro
T
Pardoll
Drew M
DM
Chen
Lieping
L
Kyle
Robert A
RA
Rodriguez
Moses
M
Pease
Larry R
LR
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D017951:Antigen Presentation / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000097:blood* / Q000737:chemistry / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D007075:Immunoglobulin M; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011961:Receptors, Fc; D017452:Receptors, IgG; C035311:immunoglobulin M receptor