CD28/CTLA4-B7 interaction is dispensable for T cell stimulation by mouse mammary tumor virus superantigen but not for B cell differentiation and virus dissemination
✍ Scribed by Eric Champagne; Leonardo Scarpellino; Peter Lane; Hans Acha-Orbea
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 837 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
B cells are the primary targets of infection for mouse mammary tumor virus (MMTV). However, for productive retroviral infection, T cell stimulation through the virally‐encoded superantigen (SAG) is necessary. It activates B cells and leads to cell division and differentiation. To characterize the role of B cell differentiation for the MMTV life cycle, we studied the course of infection in transgenic mice deficient for CD28/CTLA4‐B7 interactions (mCTLA4‐Hγ1 transgenic mice). B cell infection occurred in CTLA4‐Hγ1 transgenic mice as integrated proviral DNA could be detected in draining lymph node cells early after infection by polymerase chain reaction analysis. In mice expressing I‐E, B cells were able to present the viral SAG efficiently to Vβ6^+^ T cells. These cells expanded specifically and were triggered to express the activation marker CD69. Further stages of progression of infection appeared to be defective. Kinetics experiments indicated that T and B cell stimulation stopped more rapidly than in control mice. B cells acquired an activated CD69^+^ phenotype, were induced to produce IgM but only partially switched to IgG secretion. Finally, the dissemination of infected cells to other lymph nodes and spleen was reduced and the peripheral deletion of Vβ6^+^ T cells was minimal. In contrast, in mice lacking I‐E, T cell stimulation was also impaired and B cell activation undetectable. These data implicate B7‐dependent cellular interactions for superantigenic T cell stimulation by low‐affinity TCR ligands and suggest a role of B cell differentiation in viral dissemination and peripheral T cell deletion.