Correlation of tolerogenicity of a viral antigen with its immunogenicity.
Induction of B cell tolerance or activation was analyzed with vesicular stomatitis virus (VSV) glycoprotein (G) expressed as a neo-self Ag. A membrane form of VSV-G expressed in all tissues, including the bone marrow, induced unresponsiveness at both the Th and B cell level, whereas a soluble form of VSV-G expressed peripherally in liver and kidney did not tolerize B cells and only reversibly anergized Th cells. Interestingly, a similar correlation was found for activation of mature lymphocytes. When mature normal spleen cells were transferred into the two transgenic mouse lines, the membrane form of VSV-G was strongly immunogenic for both Th and B cells, and high VSV-G-specific IgG Ab titers were induced in these transgenic mice. In contrast, spleen cells transferred into mice expressing the soluble form of VSV-G were not activated, and no VSV-G specific Abs were induced. These results indicate that highly immunogenic Ags are strongly tolerogenic for both immature B and T cells.
Bachmann
M F
MF
Institute for Experimental Immunology, Department of Pathology, University of Zurich, Switzerland.
Fehr
T
T
Freer
G
G
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008822:Mice, Transgenic; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D000956:Antigens, Viral; C028391:G protein, vesicular stomatitis virus; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins