Targeting antigen to CD19 on B cells efficiently activates T cells.
CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells.
Yan
Jun
J
Section of Rheumatology, Department of Internal Medicine, Ludwig Institute for Cancer Research, Yale University School of Medicine, 300 Cedar Street, S525, PO Box, 208031 New Haven, CT 06520-8031, USA.
Wolff
Martin J
MJ
Unternaehrer
Julia
J
Mellman
Ira
I
Mamula
Mark J
MJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen; D051940:B7-2 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D007075:Immunoglobulin M / Q000276:immunology; D007152:Immunologic Capping / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018941:Antigens, CD19; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d