In:
Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3278-3278
Kurzfassung:
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. Disclosures: No relevant conflicts of interest to declare.
Materialart:
Online-Ressource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V120.21.3278.3278
Sprache:
Englisch
Verlag:
American Society of Hematology
Publikationsdatum:
2012
ZDB Id:
1468538-3
ZDB Id:
80069-7