Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells
Marc A. Weniger, … , Martin-Leo Hansmann, Ralf Küppers
Marc A. Weniger, … , Martin-Leo Hansmann, Ralf Küppers
Published July 2, 2018; First published June 11, 2018
Citation Information: J Clin Invest. 2018;128(7):2996-3007. https://doi.org/10.1172/JCI95993.
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Research Article Hematology Immunology

Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells

Abstract

Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human CD30+ B cells. Phenotypic and IgV gene analyses indicated that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ EF B cells are mostly post-GC B cells. The transcriptomes of CD30+ GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. CD30+ GC B cells represent MYC+ centrocytes redifferentiating into centroblasts; CD30+ EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with CD30+ B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal CD30+ B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity.

Authors

Marc A. Weniger, Enrico Tiacci, Stefanie Schneider, Judith Arnolds, Sabrina Rüschenbaum, Janine Duppach, Marc Seifert, Claudia Döring, Martin-Leo Hansmann, Ralf Küppers

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Figure 2

Unsupervised hierarchical clustering and PCA of normal human B cell subsets.

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Unsupervised hierarchical clustering and PCA of normal human B cell subs...
(A) Unsupervised hierarchical clustering was performed on 683 probe sets with SD ≥ 1. For calculating the distance matrix we used the Manhattan distance method. The dendrogram was generated with the average linkage method from the R package geneplotter. (B) PCA was conducted on 683 probe sets with SD ≥ 1. The figure shows the first 2 principal components. The first principal component covers 61.8% of the variance, the second one 17.6%. (C) Supervised PCA was performed using 229 differentially expressed probe sets with FC ≥ 4 or ≤ –4 and FDR ≤ 0.05 between GC and naive B cells. (D) Supervised PCA was performed using 128 differentially expressed probe sets with FC ≥ 4 or ≤ –4 and FDR ≤ 0.05 between conventional GC and memory B cells. (E) Supervised PCA was performed using 130 differentially expressed probe sets with FC ≥ 4 or ≤ –4 and FDR ≤ 0.05 between GC B cells and plasma cells. In B–E, the first 2 principal components are shown. Conv. GC, conventional GC B cells; PC, plasma cells; PC1/PC2, principal component 1/2.