T-CELL-INDEPENDENT IMMUNOGLOBULIN-G RESPONSES IN-VIVO ARE ELICITED BYLIVE-VIRUS INFECTION BUT NOT BY IMMUNIZATION WITH VIRAL-PROTEINS OR VIRUS-LIKE PARTICLES

Immunoglobulin G (IgG) responses to viruses are generally assumed to b e T-cell dependent (TD), Recently, however, polyomavirus (PyV) infecti on of T-cell-deficient (T-cell receptor beta chain [TCR-beta] -/- or T CR-beta x delta -/-) mice was shown to elicit a protective, T-cell-ind ependent (T1) antiviral IgM and IgG response. A repetitive, highly org anized antigenic structure common to many TI antigens is postulated to be important in the induction of antibody responses in the absence of helper T cells, To test whether the repetitive structure of viral ant igens is essential and/or sufficient for the induction of TI antibodie s, we compared the abilities of three forms of PyV antigens to induce IgM and IgG responses in T-cell-deficient mice: soluble capsid antigen s (VP1), repetitive virus-like particles (VLPs), and live PyV. Immuniz ation with each of the viral antigens resulted in IgM production. VLPs and PyV elicited 10-fold-higher IgM titers than VP1, indicating that the highly organized, repetitive antigens are more efficient in IgM in duction, Antigen-specific TI IgG responses, however, were detected onl y in mice infected with live PyV, not in VP1- or VLP-immunized mice. T hese results suggest that the highly organized, repetitive nature of t he viral antigens is insufficient to account for their ability to elic it TI IgG response and that signals generated by live-virus infection may be essential for the switch to IgG production in the absence of T cells. Germinal centers were not observed in T-cell-deficient PyV-infe cted mice, indicating that the germinal center pathway of B-cell diffe rentiation is TD even in the context of a virus infection.