Effect of B cell receptor class-switching on lymphoma cells

Although immunoglobulin class-switching from IgM to IgG enhances B cell receptor (BCR) signalling and antibody responses, certain subsets of B cell lymphomas retain unswitched IgM BCRs despite signs of class-switching in the immunoglobulin heavy chain loci. This suggests that expression of the IgG BCR suppresses progression of specific lymphoma subsets. We found that inducing BCR class switching from IgM to IgG1 or IgG4 inhibits proliferation of EZB DLBCL lymphoma cell lines. To understand changes associated with class-switching we compared transcritional profiles of isogenic WSU-FSCCL and NU-DHL1 cell lines artificially class-switched to express IgM and IgG1 BCRs. In addition, we analysed transcriptional profiles of IgG1+ cell lines into which we introduced the IgG1 W375* mutation that truncates the intracellular IgG tail. Overall design: RNASeq was performed on NU-DHL1 IgM+, NU-DHL1 IgG1+ wildtype, NU-DHL1 IgG1+ W375*, WSU-FSCCL IgG1+ wildtype, and WSU-FSCCL IgG1+ W375*cells