Interleukin-21-Induced Granzyme B-Expressing B Lymphocytes Infiltrate Tumors and Regulate T Cells

Abstract 3278

The role of B cells in tumor infiltrations is controversial. Different studies suggest that certain tumor-infiltrating B cell populations exhibit regulatory potential. Here, we demonstrate that the microenvironment of various solid tumors contains granzyme B (GrB)-expressing B cells adjacent to IL-21-providing T cells. GrB-mediated effector T cell modulation is already known from regulatory T cells (T_reg) and plasmacytoid dendritic cells. We now show that IL-21 induces B cells to express high levels of GrB and to modulate T cell proliferation by GrB-dependent degradation of the T cell receptor z-chain. Detailed characterization of IL-21-induced GrB⁺ B cells reveals a CD19⁺CD38⁺CD1d⁺CD147⁺ phenotype and expression of additional regulatory molecules including IL-10, IDO and CD25. Of note, GrB induction is accompanied by both BCR- and TLR-mediated signals and GrB expression levels are influenced by B cell expression of CD5. In summary, we demonstrate that IL-21 induces GrB-expressing regulatory B cells, which are detected in tumor infiltrations, and which may contribute to the modulation of cellular adaptive immune responses by T_reg-like mechanisms. Our findings may stimulate the development of novel diagnostic and cell therapeutic approaches to the management of malignant, autoimmune and graft-versus-host pathologies.