Translocations into human chromosome 14 JH region: factors influencing downstream abortive immunoglobulin class switching

Bcl-2 translocations in follicular lymphomas (FL) are often associated with downstream immunoglobulin class switch recombination (CSR) on the translocated allele. We studied cell lines with different translocations into the IgH locus to gauge any common features associated with downstream CSR events. CSR associated with chromosomal rearrangements was observed in cells (RL) with translocations similar to those frequently observed in FL (bcl-2-JH), and such CSR was also seen with a myc (near exon 1)-JH5 intron translocation (MC116), but not for far 5'-myc-JH5 intron (P3HR-1) or myc-Smu translocations (Ramos). Both MC116 and P3HR-1 myc translocations showed evidence for an origin from somatic hypermutation. Therefore, the association of JH translocations with CSR on the translocated allele is unlikely to be linked with specific translocation mechanisms, and the P3HR-1 configuration indicated that the downstream class switching is not a necessary consequence of (or precondition for) such a translocation event. MC116 and RL, but not P3HR-1 cells, showed constitutive transcription through the translocated IgH alleles, suggesting that transcription through this region or the processing of such transcripts may promote CSR. However, while CSR events clearly occurred in the precursors of MC116 and RL, neither cell line could undergo complete class switching.