Initiation of plasma-cell differentiation is independent of the transcription factor Blimp-1
- Kallies, A; Hasbold, J; Fairfax, K; Pridans, C; Emslie, D; McKenzie, BS; Lew, AM; Corcoran, LM; Hodgkin, PD; Tarlinton, DM; Nutt, SL;
Publication Year 2007-05, Volume 26, Issue #5, Page 555-566
- Journal Title
- Publication Type
- Journal Article
- Blimp-1 is considered an essential regulator of the terminal differentiation of B cells into antibody-secreting plasma cells. We show here that Rag1(-/-) mice reconstituted with fetal liver cells homozygous for a DNA-binding-deficient mutant of Prdm1 (the gene encoding Blimp-1) lack a defined plasma-cell compartment, yet show detectable amounts of all immunoglobulin isotypes. In vitro analysis revealed that Blimp-1 is not required for the initiation of antibody secretion but is essential for subsequent high immunoglobulin production. Blimp-1-independent differentiation was blocked at a pre-plasmablast stage characterized by decreased Pax5 expression and the activation of plasma-cell genes. Analysis of Blimp-1-sufficient differentiation revealed a phase prior to Blimp-1 expression in which several genes normally repressed by Pax5 are re-expressed, suggesting that plasma-cell differentiation is initiated by the inhibition of Pax5 function. Our results indicate that full plasma-cell differentiation but not commitment to the plasma-cell fate requires the expression of functional Blimp-1.
- CELL PRESS
- RESTING B-CELLS; GENE-EXPRESSION; LYMPHOCYTE DIFFERENTIATION; SECRETING CELLS; FACTOR XBP-1; MATURE B; REPRESSION; PROTEIN; PAX5; MATURATION
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Creation Date: 2007-05-01 12:00:00Last Modified: 0001-01-01 12:00:00