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

Eva Szomolanyi-Tsuda, James D. Brien, Jill E. Dorgan, Robert L. Garcea, Robert T. Woodland, Raymond M. Welsh

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Polyomavirus (PyV) infection induces protective T-cell-independent (TI) IgM and IgG responses in T-cell-deficient (TCR β×δ-/-) mice. In this study, we show that PyV is a TI-2 antigen: B cells with a mutated Bruton's tyrosine 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 responses against a viral infection induced in mice lacking T and NK cells (CD3Etg). Comparison of the antibody responses observed in T- and NK-cell-deficient mice with those of mice lacking only T cells, however, suggests that NK cells may promote isotype switching to IgG2a. This effect is probably mediated by IFNγ secretion. In support of this idea, studies on the antibody responses of PyV-infected SCID mice that had been reconstituted with IFNγR-/- B cells or wild-type B cells demonstrated the IFNγ dependence of PyV-specific TI IgG2a secretion and provided evidence that IFNγ acting directly on B cells plays an important role in TI pathways of isotype switching to IgG2a in vivo.

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalVirology
Volume280
Issue number2
DOIs
StatePublished - Feb 15 2001

Bibliographical note

Funding Information:
We thank Quang P Le and Jie Yin for expert technical assistance. This research was supported by Public Health Service Grants CA-66644 (to E. Szomolanyi-Tsuda), CA-37667 (to R. L.Garcea), AI-41054 (to R.T.W.), and CA-34461 (to R. M.Woodland.) from the National Cancer Institute and the National Institute of Allergy and Infectious Disease. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute, or the National Institute of Allergy and Infectious Disease.

ASJC Scopus subject areas

  • Virology

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