Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies

被引:51
作者
Hangartner, L [1 ]
Senn, BM
Ledermann, B
Kalinke, U
Seiler, P
Bucher, E
Zellweger, RM
Fink, K
Odermatt, B
Bürki, K
Zinkernagel, RM
Hengartner, H
机构
[1] Univ Zurich Hosp, Inst Expt Immunol, Dept Pathol, CH-8091 Zurich, Switzerland
[2] Univ Zurich Hosp, Inst Clin Pathol, Dept Pathol, CH-8091 Zurich, Switzerland
[3] Univ Zurich, Inst Lab Anim Sci, CH-8057 Zurich, Switzerland
[4] Paul Ehrlich Inst, Dept Immunol, D-63225 Langen, Germany
[5] Max Planck Inst Infect Biol, D-10117 Berlin, Germany
关键词
D O I
10.1073/pnas.2135542100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Naive vesicular stomatitis virus-specific Ig heavy chain transgenic mice displayed greatly elevated natural antibody titers. However, despite these high naive titers, de novo activation of naive CD4(+) T and B cells was not blocked. Therefore, B cells giving rise to natural antibodies do not participate in virus-induced antibody responses.
引用
收藏
页码:12883 / 12888
页数:6
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