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

• Published in: Blood 2012-11, Vol.120 (21), p.3278-3278
• Main Authors: Lindner, Stefanie, Dahlke, Karen, Sontheimer, Kai, Hagn, Magdalena, Kaltenmeier, Christof, Barth, Thomas F.E., Beyer, Thamara, Reister, Frank, Fabricius, Dorit, Lotfi, Ramin, Lunov, Oleg, Nienhaus, Ulrich, Simmet, Thomas, Kreienberg, Rolf, Moeller, Peter, Schrezenmeier, Hubert, Jahrsdörfer, Bernd
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.3278.3278

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 (Treg) 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 Treg-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. No relevant conflicts of interest to declare.