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Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL
- Source :
- The Journal of Experimental Medicine; May 2024, Vol. 221 Issue: 5 pe20230941-e20230941, 1p
- Publication Year :
- 2024
-
Abstract
- Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-κB activation, which can be explained by activating mutations of the BCR signaling cascade in a minority of cases. We demonstrate that autonomous BCR signaling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signaling in ABC-DLBCL. 13 of 18 tested DLBCL-derived BCR, including 12 cases selected for expression of IgM, induced spontaneous calcium flux and increased phosphorylation of the BCR signaling cascade in murine triple knockout pre-B cells without antigenic stimulation or external BCR crosslinking. Autonomous BCR signaling was associated with IgM isotype, dependent on somatic BCR mutations and individual HCDR3 sequences, and largely restricted to non-GCB DLBCL. Autonomous BCR signaling represents a novel immunological oncogenic driver mechanism in DLBCL originating from individual BCR sequences and adds a new dimension to currently proposed genetics- and transcriptomics-based DLBCL classifications.
Details
- Language :
- English
- ISSN :
- 00221007 and 15409538
- Volume :
- 221
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- The Journal of Experimental Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs65816029
- Full Text :
- https://doi.org/10.1084/jem.20230941