T-cell independent IgM and enduring protective IgG antibodies induced by chimeric measles viruses

被引:40
作者
Fehr, T
Naim, HY
Bachmann, MF
Ochsenbein, AF
Spielhofer, P
Bucher, E
Hengartner, H
Billeter, MA
Zinkernagel, RM
机构
[1] Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland
[2] Univ Zurich Honggerberg, Inst Mol Biol 1, CH-8093 Zurich, Switzerland
关键词
D O I
10.1038/nm0898-945
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
B-cell activation depends on the intensity of B-cell receptor cross-linking. Studies of haptenated antigens' and vesicular stomatitis virus(2) (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(3). 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 E-cell activation by two prototypic human pathogenic viruses and for the design of new recombinant vaccines.
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页码:945 / 948
页数:4
相关论文
共 25 条
[1]   FORMALIN INACTIVATION OF VESICULAR STOMATITIS-VIRUS IMPAIRS T-CELL- BUT NOT T-HELP-INDEPENDENT B-CELL RESPONSES [J].
BACHMANN, MF ;
KUNDIG, TM ;
KALBERER, CP ;
HENGARTNER, H ;
ZINKERNAGEL, RM .
JOURNAL OF VIROLOGY, 1993, 67 (07) :3917-3922
[2]   Neutralizing antiviral B cell responses [J].
Bachmann, MF ;
Zinkernagel, RM .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :235-270
[3]   T helper cell-independent neutralizing B cell response against vesicular stomatitis virus: Role of antigen patterns in B cell induction? [J].
Bachmann, MF ;
Hengartner, H ;
Zinkernagel, RM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (12) :3445-3451
[4]   The influence of virus structure on antibody responses and virus serotype formation [J].
Bachmann, MF ;
Zinkernagel, RM .
IMMUNOLOGY TODAY, 1996, 17 (12) :553-558
[5]   IMMUNOGENICITY OF A VIRAL MODEL VACCINE AFTER DIFFERENT INACTIVATION PROCEDURES [J].
BACHMANN, MF ;
BAST, C ;
HENGARTNER, H ;
ZINKERNAGEL, RM .
MEDICAL MICROBIOLOGY AND IMMUNOLOGY, 1994, 183 (02) :95-104
[6]  
BORCA MV, 1986, IMMUNOLOGY, V59, P261
[7]   A THEORY OF SELF-NONSELF DISCRIMINATION [J].
BRETSCHER, P ;
COHN, M .
SCIENCE, 1970, 169 (3950) :1042-+
[8]   THYMUS DEPENDENCE OF VIRAL ANTIGENS [J].
BURNS, WH ;
BILLUPS, LC ;
NOTKINS, AL .
NATURE, 1975, 256 (5519) :654-666
[9]  
CHARAN S, 1986, J IMMUNOL, V136, P3057
[10]  
DINTZIS RZ, 1983, J IMMUNOL, V131, P2196