PRDM1

BLIMP-1 is an important regulator of plasma cell differentiation. Except for naïve and memory B cells, all antibody secreting cells express BLIMP-1 regardless of their location and differentiation history. In the absence of BLIMP-1, proliferating B cells are unable to differentiate to plasma cells, resulting in severe reduction in production of all isotypes of immunoglobulin. [5]

The increased expression of the Blimp-1 protein in B lymphocytes, T lymphocytes, NK cell and other immune system cells leads to an immune response through proliferation and differentiation of antibody secreting plasma cells. Blimp-1 is also considered a 'master regulator' of hematopoietic stem cells.[7][8] Other cells of the immune system such as human peripheral blood monocytes and granulocytes also express BLIMP-1. In a monocytic cell line, over-expression of BLIMP-1 can lead to differentiation into mature macrophages. BLIMP-1 also plays a role in osteoclastogenesis as well as in the modulation of dendritic cells.

As a transcriptional repressor, BLIMP-1 has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. BLIMP-1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. The genetic lineage-tracing experiments indicate that the BLIMP-1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.[9]

During B cell development, a B cell can either differentiate into a short-lived plasma cell or into a germinal center B cell after receiving proper activation and co-stimulation. BLIMP-1 acts as a master gene regulating the transcriptional network that regulates B cell terminal differentiation. BLIMP-1 expression is carefully controlled, since premature expression of it in primary B cells results in cell death. Thus, only cells that are ready to initiate transcription driven by BLIMP-1 are able to survive and differentiate.[5][10]

BLIMP-1 plays a key role in maintaining normal T cell homeostasis. It regulates T cell responsiveness through repression of IL-2 cytokine in a negative feedback loop. T cell activation results in production of IL-2. IL-2 signaling then leads to PRDM1 transcription and BLIMP-1 feeds back to repress IL-2 gene transcription.[5]

BLIMP-1 helps the production of short-lived effector T cells and clonally exhausted T cells. It also helps with the migration of T cells out of the spleen and lymph nodes into peripheral tissues. However, BLIMP-1 does not promote the production of long-lived effector memory cells. BLIMP-1 allows the production of some longer lived effector memory cells but its absence allows for the generation of long term central memory cells, which are thought to have a higher potential of proliferation on secondary challenge.[11]  

A genome-wide association study has identified two genetic variations near the PRDM1 gene that predict an increased likelihood of developing a second cancer after radiation treatment for Hodgkin lymphoma.[12]

• PRDM1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook PRDM1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.