BCL10 Gain-of-Function Impairs Germinal Center Participation by Naive B Cells and Cooperates with BCL6 to Drive Extrafollicular Diffuse Large B-Cell Lymphoma

BCL10 gain-of-function in naive B cells blocks germinal center participation and enables transformation to DLBCL with a non-GC phenotype, linked to extrafollicular memory expansion.

• Why it matters: BCL10 GoF is found in BN2/C1 DLBCL and activates CBM signaling, yet how it shapes disease development and cooperates with other oncogenes is unclear.
• What they did: The study used single-cell analyses of premalignant B-cell populations in mouse models and corresponding human tumors, and tested co-activation with BCL6 translocation.
• The result: Co-activation of BCL10 GoF and BCL6 promotes pronounced oncogenic synergy, and extrafollicular memory B-cell programs persist in resulting lymphomas, defining a role for BCL10 activating mutations in BCL6 lymphomagenesis.

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