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

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posted on 2023-08-23, 04:09 authored by Z Ding, I Quast, F Yan, Yang LiaoYang Liao, C Pitt, K O-Donnell, MJ Robinson, Wei ShiWei Shi, A Kallies, D Zotos, DM Tarlinton
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 the development of B cell lymphoma 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 signaling, 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.


DMT was funded by National Health and Medical Research Council (NHMRC) Australia Investigator Award (APP1175411), DZ and AK by an NHMRC Project Grant (1085156), ZD by an International Postdoc Fellowship from the Swedish Research Council (2016-06659), IQ by an Early Postdoc Mobility fellowship (P2ZHP3_164964) and an Advanced Postdoc Mobility fellowship (P300PA_177893) provided by the Swiss National Science Foundation and a Peter Doherty Early Career fellowship (APP1145136) provided by NHMRC Australia, MJR by an NHMRC Ideas Grant (APP1185294), and FY by a Monash Bridging Postdoctoral Fellowship.


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Immunology and Cell Biology






13p. (p. 705-717)





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© 2022 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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