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.

Genetic alterations in B cell lymphoma subtypes as potential biomarkers for non-invasive diagnosis, prognosis, therapy, and disease monitoring

“…However, until recently, the cell of origin of HRS cells in HL was not clear. A recent study by Weniger et al showed that the transcriptomic profile of HRS cells is highly similar to that of CD30 + B cells, a rare B cell subset inside germinal centers (Weniger et al, 2018). In the same study, the transcriptional differences between the CD30 + B cell subset and HRS cells of HL were compared, and this showed significant downregulation of genomic stability regulators and cytokinesis.…”

Genomic analyses of flow-sorted Hodgkin Reed-Sternberg cells reveal complementary mechanisms of immune evasion

“…[1][2][3] HRS cells are derived from crippled, largely CD30 1 , pre-apoptotic germinal center (GC) B cells that lack functional B-cell receptors (BCRs) and have reduced expression of multiple B-cell transcription factors. 1,4 These tumor cells rely on alternative signaling and survival pathways, including JAK/STAT and nuclear factor kB (NF-kB), and exhibit genetic alterations of select pathway components. 1,[5][6][7][8][9][10] In 30% to 40% of cHLs in North America and Europe, the malignant HRS cells have evidence of latent Epstein-Barr virus (EBV) infection and associated expression of latent membrane protein 1 (LMP1) and latent membrane protein 2A (LMP2A).…”

TRAF3 as a Multifaceted Regulator of B Lymphocyte Survival and Activation

“…Small numbers of human tonsillar mononuclear cells are CD30 + B cells. These cells appear to be a subpopulation of B cells that develop during normal germinal center reactions in lymphoid tissue, and share some transcriptional patterns with Hodgkin lymphoma cells ( 43 ). In non-B cell systems, CD30 can bind TRAFs 1, 2, and 3 ( 44 , 45 ).…”