Abstract
B cell differentiation is controlled by a complex network of lineage-restricted transcription factors. How perturbations to this network alter B cell fate remains poorly understood. Here we show that classical Hodgkin lymphoma tumor cells, which originate from mature B cells, have lost the B cell phenotype as a result of aberrant expression of transcriptional regulators. The B cell-specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2. Both factors antagonized the function of the B cell-determining transcription factor E2A. As a result, expression of genes specific to B cells was lost and expression of genes not normally associated with the B lineage was upregulated. These data demonstrate the plasticity of mature human lymphoid cells and offer an explanation for the unique classical Hodgkin lymphoma phenotype.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
B-Lymphocytes / immunology
-
B-Lymphocytes / metabolism*
-
B-Lymphocytes / pathology
-
Base Sequence
-
Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
-
Basic Helix-Loop-Helix Transcription Factors / genetics
-
Basic Helix-Loop-Helix Transcription Factors / metabolism*
-
Cell Line, Tumor
-
Dimerization
-
Gene Expression
-
Hodgkin Disease / genetics
-
Hodgkin Disease / immunology
-
Hodgkin Disease / metabolism*
-
Hodgkin Disease / pathology
-
Humans
-
Inhibitor of Differentiation Protein 2 / genetics
-
Inhibitor of Differentiation Protein 2 / metabolism*
-
Multiprotein Complexes
-
PAX5 Transcription Factor / genetics
-
PAX5 Transcription Factor / metabolism
-
Phenotype
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
RNA, Neoplasm / genetics
-
RNA, Neoplasm / metabolism
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
ID2 protein, human
-
Inhibitor of Differentiation Protein 2
-
MSC protein, human
-
Multiprotein Complexes
-
PAX5 Transcription Factor
-
PAX5 protein, human
-
RNA, Messenger
-
RNA, Neoplasm
-
TCF3 protein, human