Analyses of Effector and Suppressive B Cell Populations in Head and Neck Tumor Bearing Mice

Tumor infiltrating B cells influence tumor growth and therapeutic success. It seems that the B cell subpopulations in their different roles within the immune system can exert pro- and anti-tumorigenic effects on tumor growth progression through regulator and effector functions. We established a mouse model for head and neck squamous cell carcinoma and injected SCC-VII tumor cells orthotopically into the floor of the mouth. Peripheral blood, spleen and tumor infiltrating cells were isolated from tumor bearing mice and compared to healthy controls by analysis of different populations with flow cytometry, immunohistochemistry and ELISA for immunoglobulin levels. An increase of GL7+ CD95+ germinal center B cells as well as an increase of the CD39+/CD73+ B cells could be detected in the spleens as well as in tumors of tumor bearing mice compared to healthy control mice. Tumor bearing mice showed a higher level of CD3+ CD4+CXCR5+ PD1+ follicular T-helper cells than the healthy control group. These cells help activated B cells to secret antibodies and contribute to germinal center formation. In the tumor group, we were able to record a constant increase of IgM Ab concentration in the mouse serum over the course of the observation, while the concentrations of IgG1, IgG2 and IgG3 antibodies produced after isotype switch increased significantly later in the experiment. This could confirm the role of FO-B cells in affinity maturation for antibody-producing plasma cells, whereas the increased IgM titers are due to the increasing number of MZ-B cells over time, the main producers of IgM. CD39+/CD73+ surface molecules in the spleen tissue was most pronounced on MZ-B cells instead of on FO and NF-B cells, so that in our HNSCC mouse model these play an immunosuppressive role.