CD137L and CD4 T cells limit BCL6-expressing pre-germinal center B cell expansion and BCL6-driven B cell malignancy.

2022-08-02

Ding, Zhoujie

Quast, Isaak

Yan, Feng

Liao, Yang

Pitt, Catherine

O-Donnell, Kristy

Robinson, Marcus J

Shi, Wei

Kallies, Axel

Zotos, Dimitra

Tarlinton, David M

B cell malignancy

BCL6

CD137L

CD4 T cells

tumour immunity

Journal Article

0000-0001-6517-8537

0000-0001-5677-3078

0000-0001-9928-686X

10.1111/imcb.12578

Aberrant expression of the proto-oncogene BCL6 is a driver of tumorigenesis in diffuse large B cell lymphoma (DLBCL). Mice overexpressing BCL6 from the B cell-specific immunoglobulin heavy chain μ intron promoter (Iμ-Bcl6Tg/+ ) develop B cell lymphomas with features typical of human DLBCL. While B cell lymphoma development in these mice is tightly controlled by T cells, the mechanisms of this immune surveillance are poorly understood. Here we show that CD4 T cells contribute to the control of lymphoproliferative disease in lymphoma-prone Iμ-Bcl6Tg/+ mice. We reveal that this CD4 T-cell immuno-surveillance requires signaling by the co-stimulatory molecule CD137 ligand (CD137L; also known as 4-1BBL), which may promote the transition of pre-malignant B cells with an activated phenotype into the germinal center stage via reverse signalling, preventing their hazardous accumulation. Thus, CD137L-mediated CD4 T cell immuno-surveillance adds another layer of protection against B-cell malignancy to that provided by CD8 T-cell cytotoxicity.

link

Immunology and Cell Biology 2022-10; 100(9): 705-717

Immunology and Cell Biology