Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies.
Two gene-targeted immunoglobulin heavy chain transgenic mouse strains, TgH(KL25) and TgH(VI10), expressing neutralizing specificities for lymphocytic choriomeningitis virus and vesicular stomatitis virus, respectively, have been generated. Three days after lymphocytic choriomeningitis virus infection, TgH(KL25) mice showed a thymus-independent neutralizing IgM response followed by thymus-dependent (TD) IgG. In contrast, WT mice mounted only a TD IgG response around day 80. These observations indicated that not only structural properties of the virus but also immunological parameters such as the frequency of B cells were indicative for the induction of thymus-independent versus TD Ig responses. Naïve vesicular stomatitis virusspecific Ig heavy chain transgenic mice displayed greatly elevated natural antibody titers. However, despite these high naïve titers, de novo activation of naïve CD4+ T and B cells was not blocked. Therefore, B cells giving rise to natural antibodies do not participate in virus-induced antibody responses.
Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zurich, Switzerland. haegar@pathol.unizh.ch
Lars
L
Hangartner
Beatrice M
BM
Senn
Birgit
B
Ledermann
Ulrich
U
Kalinke
Peter
P
Seiler
Etienne
E
Bucher
Raphaël M
RM
Zellweger
Katja
K
Fink
Bernhard
B
Odermatt
Kurt
K
Bürki
Rolf M
RM
Zinkernagel
Hans
H
Hengartner
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009500:Neutralization Tests; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region