We have investigated antigen-independent modulation of immune response
s by monoclonal antibodies directed against both viral and nonviral an
tigens. BALB/c mice were immunized with monoclonal IgM (i.e. Ab1) spec
ific for either Moloney murine leukemia virus-induced cell surface ant
igen (MCSA) or the hapten 2,4-dinitrophenyl (DNP). Injection with eith
er Ab1 activated a functional idiotypic (Id) network as evidenced by p
roduction of both anti-Id (Ab2) antibodies and anti-anti-Id (Ab3) anti
bodies. A subset of induced Ab3 (designated Ab1'), exhibited specifici
ty for antigen (virus or DNP). In mice immunized with anti-Id antibodi
es (Ab2), production of Ab3 and Ab1' was also observed. In the MCSA. s
ystem, antibody-induced Ab1' responses were effective in protecting mi
ce from tumor development upon subsequent challenge with live virus. F
urthermore, antigen-independent modulation of immunity to bath viral a
nd nonviral antigens was found to be thymus-dependent. Similar finding
s in other viral systems suggest that antibody-induced activation of I
d networks may prove a viable alternative vaccine strategy that can el
icit antigen-specific responses, and in some cases protection, in the
apparent absence of exposure to antigen.