Antiviral T-cell-independent type 2 antibody responses induced in vivo in the absence of T and NK cells

Polyomavirus (PyV) infection induces protective T-cell-independent (TI) IgM and IgG responses in T-cell-deficient (TCR betax delta-/-) mice. In this s tudy, we show that PyV is a TI-2 antigen: B cells with a mutated Bruton's t yrosine kinase (Xid mutants) do not respond to PyV with antibody secretion in the absence of T cells. We also demonstrate that NK-cell-mediated "help" is not absolutely required for the induction of the TI-2 antibodies to PyV ; thus for the first time, we provide evidence for protective IgM and IgG r esponses against a viral infection induced in mice lacking T and NK cells ( CD3Etg). Comparison of the antibody responses observed in T- and NK-cell-de ficient mice with those of mice lacking only T cells, however. suggests tha t NK cells may promote isotype switching to IgG2a. This effect is probably mediated by IFN gamma secretion. In support of this idea, studies on the an tibody responses of PyV-infected SCID mice that had been reconstituted with IFN gammaR-/- B cells or wild-type B cells demonstrated the IFN gamma depe ndence of PyV-specific TI IgG2a secretion and provided evidence that IFN ga mma acting directly on B cells plays an important role in TI pathways of is otype switching to IgG2a in vivo. (C) 2001 Academic Press.