CD74 as a regulator of transcription in normal B cells

CD74 is receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD) that serves as a transcriptional regulator in chronic lymphocytic leukemia (CLL) cells. In the current study, we investigated the transcriptional and regulatory function of CD74-ICD in normal B cells. We show that following activation, CD74-ICD forms a complex in the cytosol with transcription factors, like PAX5, and binds the chromatin at a significantly higher number of sites compared with its binding in CLL cells. The expression of a major portion of these bound genes is shut down in the malignant cells. The CD74-ICD:PAX5 complex binds the promoter areas of a tumor-suppressor gene, DMTF1, and downregulates its expression through inhibition of transcription. These findings can help identify novel therapeutic pathways that are regulated during onco-genic transformation and are targets for future treatments.

Automated summary

This study investigated the transcriptional and regulatory function of CD74-ICD in normal B cells. It was found that CD74-ICD forms a complex with PAX5 and binds to chromatin at a higher number of sites compared to CLL cells. The CD74-ICD:PAX5 complex also downregulates the expression of the tumor-suppressor gene DMTF1 through transcriptional inhibition.