Interferon gamma-producing gammadelta T cell-dependent antibody isotype switching in the absence of germinal center formation during virus infection.
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.
Maloy
K J
KJ
Institute of Experimental Immunology, Department of Pathology, University of Zürich, Schmelzbergstrasse 12, CH-8091, Zürich, Switzerland. kmaloy@pathol.unizh.ch
Odermatt
B
B
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D003167:Complement Activation; D018858:Germinal Center / Q000276:immunology* / Q000821:virology*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000821:virology; D013280:Stomatitis / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma