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

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.

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Publication Details

Journal
Haematologica
Published
2026-06-25
DOI
https://doi.org/10.3324/haematol.2025.300248
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
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article

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

Kazuhiro Ikeuchi, Katsuyoshi Takata, Katsuma Tani, Aixiang Jiang et al.
Haematologica
CAR-T cell therapy research
article

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

Kazuhiro Ikeuchi, Katsuyoshi Takata, Katsuma Tani, Aixiang Jiang, Noboru Asada, Keisuke Seike, Hideaki Fujiwara, Kazutaka Sunami, Shuta Tomida, Daisuke Ennishi, Akira Yamamoto, Yasuharu Sato, Hiroki Kobayashi, Hideki Ujiie, Merrill Boyle, Tomohiro Urata, Kaho Kondo, Yusuke Naoi, Hiroyuki Murakami, Keiko Fujii, Hirofumi Inoue, Soichiro Fujii, Tomofumi Yano, Yasushi Hiramatsu, N Fujii, Toshi Imai, Yuichiro Nawa, Pedro Farinha, Ryota Chijimatsu, Tadashi Yoshino, Ken-ichi Matsuoka, Kazuhiko Yamamoto, Isao Yoshida, David W. Scott, Yoshinobu Maeda
article en

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.

Haematologica
BC Cancer Agency (CA), Okayama University (JP), Spinal Cord Injury BC (CA), CHI Health (US), Okayama University Hospital (JP), Okayama Red Cross General Hospital (JP), Himeji Red Cross Hospital (JP), National Hospital Organization (JP), Shikoku Cancer Center (JP), Ehime Prefectural Central Hospital (JP), Okayama Rosai Hospital (JP), Okayama Medical Center (JP), Niigata University (JP)
Good health and well-being
Openalex Percentile: Top 8%
CAR-T cell therapy research
DOIOpen Access PDFOpenAlex
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