Antigen-independent, autonomous B cell receptor signaling drives activated B cell DLBCL.
J Exp Med
; 221(5)2024 May 06.
Article
en En
| MEDLINE
| ID: mdl-38512136
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Leucemia Linfocítica Crónica de Células B
/
Linfoma de Células B Grandes Difuso
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos