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

doi:10.1073/pnas.2135542100

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

Institutes of ^*Experimental Immunology and ^**Clinical Pathology, Department of Pathology, University Hospital, CH-8091 Zurich, Switzerland; ^§Institute of Laboratory Animal Science, University of Zurich, CH-8057 Zurich, Switzerland; ^¶Department of Immunology, Paul Ehrlich Institute, D-63225 Langen, Germany; and ^∥Max Planck Institute for Infection Biology, D-10117 Berlin, Germany

Contributed by Rolf M. Zinkernagel, August 28, 2003

Abstract

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.

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: haegar{at}pathol.unizh.ch.
↵ † L.H. and B.M.S. contributed equally to this work.
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CTL, cytotoxic T lymphocytes; IgH, Ig heavy chain; IND, serotype Indiana; LCMV, lymphocytic choriomeningitis virus; pfu, plaque-forming units; TI, thymus independent; VSV, vesicular stomatitis virus.