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/

B cells are the primary targets of infection for mouse mammary tumor v irus (MMTV). However, for productive retroviral infection, T cell stim ulation through the virally-encoded superantigen (SAG) is necessary. I t activates B cells and leads to cell division and differentiation. To characterize the role of B cell differentiation for the MMTV life cyc le, we studied the course of infection in transgenic mice deficient fo r CD28/CTLA4-B7 interactions (mCTLA4-H gamma 1 transgenic mice). B cel l infection occurred in CTLA4-H gamma 1 transgenic mice as integrated proviral DNA could be detected in draining lymph node cells early afte r infection by polymerase chain reaction analysis. In mice expressing I-E, B cells were able to present the viral SAG efficiently to V beta 6(+) T cells. These cells expanded specifically and were triggered to express the activation marker CD69. Further stages of progression of i nfection 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 produc e IgM but only partially switched to IgG secretion. Finally, the disse mination of infected cells to other lymph nodes and spleen was reduced and the peripheral deletion of V beta 6(+) T cells was minimal. In co ntrast, in mice lacking I-E, T cell stimulation was also impaired and B cell activation undetectable. These data implicate B7-dependent cell ular interactions for superantigenic T cell stimulation by low-affinit y TCR ligands and suggest a role of B cell differentiation in viral di ssemination and peripheral T cell deletion.