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.