Kallies Axel, Hasbold Jhagvaral, Fairfax Kirsten, Pridans Clare, Emslie Dianne, McKenzie Brent S, Lew Andrew M, Corcoran Lynn M, Hodgkin Philip D, Tarlinton David M, Nutt Stephen L
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Immunity. 2007 May;26(5):555-66. doi: 10.1016/j.immuni.2007.04.007.
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 preplasmablast 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.
Blimp-1被认为是B细胞终末分化为分泌抗体的浆细胞的关键调节因子。我们在此表明，用编码Blimp-1的基因Prdm1的DNA结合缺陷型突变体纯合的胎肝细胞重建的Rag1-/-小鼠缺乏明确的浆细胞区室，但仍显示出可检测到的所有免疫球蛋白同种型。体外分析表明，抗体分泌的起始不需要Blimp-1，但对于随后高免疫球蛋白的产生至关重要。不依赖Blimp-1的分化在一个前浆细胞阶段受阻，其特征是Pax5表达降低和浆细胞基因激活。对Blimp-1充足的分化分析揭示了一个在Blimp-1表达之前的阶段，在此阶段一些通常被Pax5抑制的基因重新表达，这表明浆细胞分化是由Pax5功能的抑制引发的。我们的结果表明，完全的浆细胞分化而非浆细胞命运的决定需要功能性Blimp-1的表达。
