T-cell independent IgM and enduring protective IgG antibodies induced by chimeric measles viruses.
B-cell activation depends on the intensity of B-cell receptor cross-linking. Studies of haptenated antigens and vesicular stomatitis virus (VSV) have demonstrated a correlation between antigen repetitiveness and the degree to which B-cell activation is independent of T cells. Here, we compare neutralizing antibody responses to inactivated VSV with those to two inactivated human pathogenic viruses: highly cytopathic poliovirus (PV) and poorly cytopathic measles virus (MV). The rigidly structured PV efficiently induced neutralizing IgM antibodies independent of T cells. In contrast, neutralizing antibodies to the pleomorphic MV were dependent on helper T cells. To test whether this resulted from the differences in virus structure or the capacity of MV to induce cell fusion and/or immunosuppression, we analyzed antibody responses to chimeric MV expressing VSV glycoprotein instead of MV fusion protein and hemagglutinin. IgM antibodies were independent of T cells; in addition, we found IgG responses dependent on T-cell help that were enduring and protective against lethal VSV infection. Because chimeric MV viruses look like MV ultrastructurally, we conclude that not only structural differences in the envelope but also the ability of MV to induce immunosuppression may limit its capacity to directly activate B cells. These findings are relevant for our understanding of B-cell activation by two prototypic human pathogenic viruses and for the design of new recombinant vaccines.
Institute of Experimental Immunology, University Hospital, Zürich, Switzerland.
T
T
Fehr
H Y
HY
Naim
M F
MF
Bachmann
A F
AF
Ochsenbein
P
P
Spielhofer
E
E
Bucher
H
H
Hengartner
M A
MA
Billeter
R M
RM
Zinkernagel
D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008212:Lymphocyte Depletion; D008459:Measles virus / Q000235:genetics* / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009500:Neutralization Tests; D017955:Poliovirus / Q000235:genetics / Q000276:immunology*; D012328:RNA Viruses / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014466:Ultraviolet Rays; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M