Immunoglobulin class-switch recombination occurs in mantle cell lymphomas.
Mantle cell lymphoma (MCL) is an IgM-expressing B cell lymphoma that originates from naive B cells and responds poorly to chemotherapy. We show here that several MCLs harbour isotype-switched subclones. Similar to the situation in normal B cells, in vitro stimulation of MCL cell lines with CD40 ligand (CD40L) and interleukin-4 induced expression of activation-induced cytidine deaminase (AID) and germline transcription at the immunoglobulin heavy chain gene locus. Additionally, the occurrence of switch-circle transcripts and mature IgG transcripts after stimulation indicated ongoing class-switch recombination in mantle cell lymphoma cell lines. Furthermore, stimulation of primary MCL cells in vitro induced expression of class-switched IgG mRNA in the tumour cells. Our data indicate that mantle cell lymphomas have retained the ability to undergo class-switch recombination if appropriate stimuli, such as the CD40 ligand, are provided.
Klapper
W
W
Department of Haematopathology and Lymph Node Registry Kiel, Schleswig-Holstein University Hospitals, Campus Kiel, Niemannsweg 11, 24105 Kiel, Germany.
Szczepanowski
M
M
Heidorn
K
K
Müschen
M
M
Liedtke
S
S
Sotnikova
A
A
Andersen
N S
NS
Greeve
J
J
Parwaresch
R
R
D019013:CD40 Antigens / Q000276:immunology; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D015847:Interleukin-4 / Q000276:immunology; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000276:immunology; D009154:Mutation / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011995:Recombination, Genetic / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology
D019013:CD40 Antigens; D007074:Immunoglobulin G; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015847:Interleukin-4; D003564:Cytidine Deaminase