Human [CD30.sup.+] 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.sup.-]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.sup.+] B cells. Phenotypic and IgV gene analyses indicated that [CD30.sup.+] GC B lymphocytes represent typical GC B cells, and that [CD30.sup.+] EF B cells are mostly post-GC B cells. The transcriptomes of [CD30.sup.+] 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.sup.+] GC B cells represent [MYC.sup.+] centrocytes redifferentiating into centroblasts; [CD30.sup.+] EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with [CD30.sup.+] B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal [CD30.sup.+] 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.