Early neutralizing antibody response against mouse mammary tumor virus: critical role of viral infection and superantigen-reactive T cells.
Infectious mouse mammary tumor virus (MMTV) is a retrovirus that expresses a superantigen shortly after infection of B cells. The superantigen first drives the polyclonal activation and proliferation of superantigen-reactive CD4+ T cells, which then induce the infected B cells to proliferate and differentiate. Part of the MMTV-induced B cell response leads to the production of Abs that are specific for the viral envelope protein gp52. Here we show that this Ab response has virus-neutralizing activity and confers protection against superinfection by other MMTV strains in vivo as soon as 4 to 7 days after infection. A protective Ab titer is maintained lifelong. Viral infection as well as the superantigen-induced T-B collaboration are required to generate this rapid and long lasting neutralizing Ab response. Polyclonal or superantigen-independent B cell activation, on the contrary, does not lead to detectable virus neutralization. The early onset of this superantigen-dependent neutralizing response suggests that viral envelope-specific B cells are selectively recruited to form part of the extrafollicular B cell response and are subsequently amplified and maintained by superantigen-reactive Th cells.
Luther
S A
SA
Ludwig Institute for Cancer Research, Lausanne Branch, Switzerland.
Maillard
I
I
Luthi
F
F
Scarpellino
L
L
Diggelmann
H
H
Acha-Orbea
H
H
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D007109:Immunity; D008213:Lymphocyte Activation / Q000276:immunology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012192:Retroviridae Infections / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*
D000914:Antibodies, Viral; D018089:Superantigens