Motyka B, Reynolds J D
Department of Medical Physiology, University of Calgary, Alberta, Canada.
Immunology. 1995 Mar;84(3):383-7.
The major site of B-cell genesis in the sheep is the ileal Peyer's patch (PP). The B cells in the ileal PP undergo both extensive proliferation and massive death in association with an ongoing diversification of the immunoglobulin repertoire by somatic hypermutation. Most, if not all, the B-cell death in the ileal PP is due to apoptosis. When placed in culture, ileal PP B cells undergo rapid apoptosis. Here, we investigated the expression of the proto-oncogene bcl-2 in ileal PP cells in situ and in culture. Bcl-2 expression has been correlated with the prevention of apoptosis in many cell types. Western blotting, using anti-Bcl-2 monoclonal antibodies, revealed that a Bcl-2-reactive protein of 26,000 MW was expressed in ileal mesenteric lymph node cells, splenocytes and thymocytes from sheep, but was barely detectable in ileal PP B cells in situ or in culture. However, Bcl-2 expression could be markedly induced in ileal PP B cells cultured with phorbol ester and Ca2+ ionophore, a procedure that is known to rescue these cells from apoptosis. We hypothesize that those few B cells that survive a selection event in the ileal PP may begin to express elevated levels of Bcl-2 as they escape from the apoptotic pathway.
绵羊B细胞产生的主要部位是回肠派伊尔结(PP)。回肠PP中的B细胞会经历广泛增殖和大量死亡,这与通过体细胞超突变使免疫球蛋白库不断多样化有关。回肠PP中大多数(如果不是全部)B细胞死亡是由于凋亡。当置于培养中时,回肠PP B细胞会迅速凋亡。在此,我们研究了原癌基因bcl-2在回肠PP细胞原位及培养中的表达。Bcl-2的表达已与多种细胞类型中凋亡的预防相关。使用抗Bcl-2单克隆抗体进行的蛋白质印迹分析显示,分子量为26,000的与Bcl-2反应的蛋白在绵羊的回肠系膜淋巴结细胞、脾细胞和胸腺细胞中表达,但在回肠PP B细胞原位或培养中几乎检测不到。然而,在用佛波酯和Ca2+离子载体培养的回肠PP B细胞中,Bcl-2表达可被显著诱导,这一过程已知可使这些细胞免于凋亡。我们推测,那些在回肠PP的选择事件中存活下来的少数B细胞,在它们从凋亡途径逃脱时,可能开始表达升高水平的Bcl-2。