Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Ave., Maywood, IL 60153, USA.
Blood. 2011 Apr 7;117(14):3770-9. doi: 10.1182/blood-2010-08-301119. Epub 2011 Feb 1.
B lymphopoiesis arrests in rabbits by 4 months of age. To identify molecules that contribute to this arrest, cDNA-representational difference analysis on BM stromal cells from young and adult rabbits showed that expression of Postn that encodes for the extracellular matrix protein periostin dramatically reduced with age. Postn-small interfering RNA OP9 cells lost their capacity to support B-cell development from rabbit or murine BM cells, and reexpression of periostin restored this potential, indicating an in vitro requirement for periostin in B lymphopoiesis. In our system, we determined that periostin deficiency leads to increased cell death and decreased proliferation of B-lineage progenitors. Further, RGD peptide inhibition of periostin/α(v)β(3) interaction resulted in a marked decrease in B lymphopoiesis in vitro. Microarray analysis of the Postn-small interfering RNA OP9 cells showed decreased expression of key B-lymphopoietic factors, including IL-7 and CXCL12. In vivo, unidentified molecule(s) probably compensate periostin loss because Postn(-/-) mice had normal numbers of B-cell progenitors in BM. We conclude that the decline in periostin expression in adult rabbit BM does not solely explain the arrest of B lymphopoiesis. However, the interaction of periostin with α(v)β(3) on lymphoid progenitors probably provides both proliferative and survival signals for cells in the B-cell development pathway.
B 细胞在兔子中于 4 月龄时发育停滞。为了鉴定导致这种停滞的分子,我们对幼兔和成年兔骨髓基质细胞进行了 cDNA 代表性差异分析,结果显示编码细胞外基质蛋白骨粘连蛋白的 Postn 表达随年龄显著降低。Postn-siRNA OP9 细胞丧失了支持兔或鼠骨髓细胞 B 细胞发育的能力,而骨粘连蛋白的再表达恢复了这种潜能,表明骨粘连蛋白在体外是 B 细胞发育所必需的。在我们的系统中,我们确定骨粘连蛋白缺乏会导致 B 细胞谱系祖细胞的细胞死亡增加和增殖减少。此外,RGD 肽抑制骨粘连蛋白/α(v)β(3)相互作用导致体外 B 细胞发育明显减少。Postn-siRNA OP9 细胞的微阵列分析显示,关键 B 淋系发生因子的表达减少,包括 IL-7 和 CXCL12。在体内,可能有未知的分子补偿骨粘连蛋白的缺失,因为 Postn(-/-) 小鼠的骨髓中 B 细胞祖细胞数量正常。我们的结论是,成年兔骨髓中骨粘连蛋白表达的下降不能完全解释 B 细胞发育停滞的原因。然而,骨粘连蛋白与淋巴细胞祖细胞上的 α(v)β(3)的相互作用可能为 B 细胞发育途径中的细胞提供增殖和存活信号。