ID: 42: IL-6/STAT3 Pathway in B Cell Gammaherpesvirus Latency and Myc-Driven B Cell Lymphoma

STAT3 is at the molecular crossroads of innate and adaptive immunity, and in B cells it responds to many cytokines including IL-6, IL-10, and IL-21. We investigated the role of STAT3 in two animal models of disease, the establishment of gammaherpesvirus latency in B cells, and the promotion of B cell lymphomas by the c-myc proto-oncogene. Murine gammaherpesvirus, MHV68, was used to evaluate the requirement of STAT3 for establishment of viral latency in B cells. We infected mice that lacked expression of STAT3 specifically in B cells by both intranasal and intraperitoneal routes. Establishment of viral latency in these animals was substantially impaired compared to controls, as assayed by colonization of the spleen and persistent infection of germinal center immunoglobulin class-switched B cells. There were no dramatic changes in total or virus-specific IgG titers in the absence of B cell STAT3. Our findings recognize STAT3 as a mediator of gammaherpesvirus latency in B cells. The E μ -myc transgenic mouse is a model of Burkitt’s B cell lymphoma in which elevated levels of c-Myc are expressed in the B cell lineage. We generated E μ -myc mice that either lacked the IL-6 gene, or lacked the STAT3 gene specifically in B cells to determine the role of the IL-6/STAT3 pathway in tumor development. We found that IL-6 promotes the development of E μ -myc B cell lymphomas, but the B cell intrinsic expression of STAT3 does not contribute to the development of E μ -myc lymphomas. Therefore, an IL-6-dependent signal pathway distinct from STAT3 cooperates with E μ -myc in oncogenesis.