PRDM1

PRDM1, also known as BLIMP-1 (B lymphocyte-induced maturation protein-1) and PRDI-BF1, is a transcription factor encoded by the PRDM1 gene in humans. It belongs to the PRDM family, characterized by an N-terminal PR domain and a C2H2-type zinc finger DNA-binding domain. The PR domain is related to histone methyltransferase activity, contributing to chromatin modification.

PRDM1 functions as a master regulator of terminal differentiation in B cells, promoting the plasma cell fate. It is induced during B cell activation by signals such as IL-21 and IRF4, and subsequently represses genes that maintain the B cell program, including PAX5, BCL6, and CIITA. By shutting down the germinal center program, BLIMP-1 helps drive the transition from antibody-secreting plasmablasts to mature plasma cells. PRDM1 also has roles in other immune cells, including T cells, natural killer cells, and dendritic cells, where it influences differentiation and function.

Mechanistically, BLIMP-1 acts as a transcriptional repressor by recruiting co-repressors and chromatin-modifying enzymes to target loci, enforcing repressive chromatin states. The PR domain contributes to its chromatin-modifying activities, while the zinc finger region mediates DNA binding.

Clinical significance of PRDM1 is linked to immune-related diseases and cancer. It functions as a tumor suppressor in several B-cell lymphomas, with loss or inactivation reported in diffuse large B-cell lymphoma and related malignancies, contributing to aberrant B cell differentiation. In model systems, Prdm1 deficiency impairs plasma cell formation and humoral immune responses, illustrating its essential role in humoral immunity.

See also: PRDM family; BLIMP-1; plasma cell differentiation.