Role of dendritic cells in the immune response induced by mouse mammary tumor virus superantigen.
After mouse mammary tumor virus (MMTV) infection, B lymphocytes present a superantigen (Sag) and receive help from the unlimited number of CD4(+) T cells expressing Sag-specific T-cell receptor Vbeta elements. The infected B cells divide and differentiate, similarly to what occurs in classical B-cell responses. The amplification of Sag-reactive T cells can be considered a primary immune response. Since B cells are usually not efficient in the activation of naive T cells, we addressed the question of whether professional antigen-presenting cells such as dendritic cells (DCs) are responsible for T-cell priming. We show here, using MMTV(SIM), a viral isolate which requires major histocompatibility complex class II I-E expression to induce a strong Sag response in vivo, that transgenic mice expressing I-E exclusively on DCs (I-EalphaDC tg) reveal a strong Sag response. This Sag response was dependent on the presence of B cells, as indicated by the absence of stimulation in I-EalphaDC tg mice lacking B cells (I-EalphaDC tg muMT(-/-)), even if these B cells lack I-E expression. Furthermore, the involvement of either residual transgene expression by B cells or transfer of I-E from DCs to B cells was excluded by the use of mixed bone marrow chimeras. Our results indicate that after priming by DCs in the context of I-E, the MMTV(SIM) Sag can be recognized on the surface of B cells in the context of I-A. The most likely physiological relevance of the lowering of the antigen threshold required for T-cell/B-cell collaboration after DC priming is to allow B cells with a low affinity for antigen to receive T-cell help in a primary immune response.
Baribaud
F
F
Institute of Microbiology, University of Lausanne, CH-1011 Lausanne, Switzerland. fbaribau@mail.med.upenn.edu
Maillard
I
I
Vacheron
S
S
Brocker
T
T
Diggelmann
H
H
Acha-Orbea
H
H
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*
D000956:Antigens, Viral; D018089:Superantigens