Regulation and functions of Blimp-1 in T and B lymphocytes.
B lymphocyte-induced maturation protein-1 (Blimp-1), discovered 16 years ago as a transcriptional repressor of the IFNbeta promoter, plays fundamentally important roles in many cell lineages and in early development. This review focuses on Blimp-1 in lymphocytes. In the B cell lineage, Blimp-1 is required for development of immunoglobulin-secreting cells and for maintenance of long-lived plasma cells (LLPCs). Direct targets of Blimp-1 and the transcriptional cascades Blimp-1 initiates to trigger plasmacytic differentiation are described. Blimp-1 also affects the homeostasis and function of CD4(+), CD8(+), and regulatory CD4(+) T cells, and Blimp-1 levels are highest in antigen-experienced T cells. Blimp-1 attenuates T cell proliferation and survival and modulates differentiation. Roles for Blimp-1 in Th1/Th2 specification, regulatory T cell function, and CD8 differentiation and function are under investigation. Signals that induce Blimp-1 in B cells include Toll-like receptor ligands and cytokines; in T cells, T cell receptors and cytokines induce Blimp-1. In spite of some commonalities, different targets and regulators of Blimp-1 in B and T cells suggest intriguing evolutionary divergence of this regulatory machinery.
Martins
Gislâine
G
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. gm2141@columbia.edu
Calame
Kathryn
K
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation; D006801:Humans; D051379:Mice; D008954:Models, Biological; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1