Gradient of CD79B expression in diffuse large B-cell lymphoma corresponds to stages of germinal center B-cell differentiation

Abstract

A CD79B-targeted antibody-drug conjugate, polatuzumab-vedotin has significantly improved outcomes in DLBCL, particularly in the activated B-cell-like (ABC) subtype. This indicates that CD79B expression varies among COO subtypes, although the expression level was not necessarily higher in ABC-DLBCL. Here, we evaluated CD79B protein expression by immunohistochemistry (IHC) in 590 de novo DLBCL cases, observing a CD79B gradient according to COO subtypes, with ABC-DLBCL showing the lowest expression, followed by GCB and dark-zone signature-positive (DZsigpos) cases in ascending order (P < 0.0001). This observation was fully validated in an independent population-based cohort of 272 cases derived from BC Cancer registry. Given that COO classification reflects the stages of normal germinal center (GC) B-cell differentiation, we further explored CD79B expression dynamics during B-cell maturation by performing single-cell proteomic and transcriptomic analyses. Analyses of 2,447 normal GC B-cells demonstrated a progressive decrease in CD79B expression as GC B-cells transitioned toward terminal differentiation. Collectively, our findings reveal a novel COO-dependent gradient of CD79B expression, particularly with lower expression in ABC-DLBCL.