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

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.