Interferon gamma-producing gammadelta T cell-dependent antibody isotype switching in the absence of germinal center formation during virus infection.

Maloy, K. J. , Odermatt, B., Hengartner, H. and Zinkernagel, R. M. (1998) Interferon gamma-producing gammadelta T cell-dependent antibody isotype switching in the absence of germinal center formation during virus infection. Proceedings of the National Academy of Sciences of the United States of America, 95(3), pp. 1160-1165. (doi: 10.1073/pnas.95.3.1160) (PMID:9448302) (PMCID:PMC18706)

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Abstract

Ig class switching usually occurs as a consequence of cognate interactions between antigen-specific B cells and CD4(+) alphabeta T cells. Vesicular stomatitis virus (VSV) infection of immunocompetent mice induces a rapid T-independent neutralizing IgM response followed by a long-lived T-dependent IgG response. Surprisingly, alphabeta T cell-deficient (TCRalpha-/-) mice also produced neutralizing IgG antibodies when infected with live VSV or with a recombinant vaccinia virus expressing the VSV glycoprotein (Vacc-IND-G), but not when immunized with UV-inactivated VSV (UV-VSV). The neutralizing IgG responses did not require the presence of NK cells or complement, but were crucially dependent on IFN-gamma and were predominantly of the IgG2a isotype. IgG production depended on residual CD3(+) non-alphabeta T cell populations present in the TCRalpha-/- mice, which produced IFN-gamma upon in vitro stimulation. A key role for gammadelta T cells was confirmed by the fact that TCRbeta-/- mice also generated strong neutralizing IgG responses to VSV, whereas TCRbeta-/-delta-/- mice produced very low titers. The neutralizing IgG responses of TCRalpha-/- mice were accompanied by the development of memory B cells, but not by antigen-specific germinal center (GC) formation. Thus, during viral infection of alphabeta T cell-deficient mice, gammadelta T cells may provide the signals that are required for isotype switching.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: Maloy, K. J., Odermatt, B., Hengartner, H., and Zinkernagel, R. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490

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