Campana D, Farrant J, Inamdar N, Webster A D, Janossy G
Department of Immunology, Royal Free Hospital School of Medicine, London, U.K.
J Immunol. 1990 Sep 15;145(6):1675-80.
In this study, we applied mAb and heterologous antisera in double marker combinations to investigate the phenotype and the proliferative activity of immature B lineage cells in XLA. Bone marrow (BM) samples from eight male adult patients with no circulating B lymphocytes were studied. The proportions and the phenotype of the earliest identifiable B cell progenitors, expressing nuclear terminal deoxynucleotidyl transferase (TdT), cytoplasmic CD22, and membrane CD19 and CD10 were identical to those observed in normal BM. In XLA these cells represented 1.2% to 22% of BM mononuclear cells; 5% to 42% and 1% to 45% of such cells weakly expressed CD20 and CD37, respectively, and invariably lacked CD13 and CD33. Cytoplasmic mu+ sIg- pre-B cells were seen in low numbers (0.1% to 0.3%) in four samples and were undetectable in the remaining four. Consequently, the ratio TdT+/c mu+ was greater than 100 in five out of eight samples studied in contrast to the less than 10 values seen in normal individuals. The proliferative activity of B lineage progenitor cells was studied by using Ki67 and anti-bromodeoxyuridine mAb. Although the proliferation of TdT+ cells in XLA was comparable with that seen in normal BM samples (24% to 59% of TdT+ were Ki67+ and 11% to 27% incorporated bromodeoxyuridine), this was dramatically reduced in the c mu+ cells (no c mu+, Ki67+ seen in three samples where pre-B cells were observed). Thus, the abnormalities of B cell differentiation in XLA are first seen at the c mu+ pre-B stage and suggest a maturation block in the transition between TdT+, c mu- pre-pre-B cells and c mu+ pre-B cells. The severity of this block may be variable, allowing the generation of a near normal number of pre-B cells in some patients, which nevertheless have a defective proliferative activity. Finally, our study further supports the concept that the effects of the "XLA gene" are confined within the B lineage by demonstrating that the proportions of T cells bearing TCR-alpha beta and TCR-gamma delta in XLA are similar to those seen in normal individuals.
在本研究中，我们应用单克隆抗体（mAb）和异源抗血清进行双标记组合，以研究X连锁无丙种球蛋白血症（XLA）中未成熟B淋巴细胞系细胞的表型和增殖活性。研究了8名无循环B淋巴细胞的成年男性患者的骨髓（BM）样本。最早可识别的B细胞祖细胞的比例和表型，即表达核末端脱氧核苷酸转移酶（TdT）、细胞质CD22、膜CD19和CD10的细胞，与正常BM中观察到的相同。在XLA中，这些细胞占BM单核细胞的1.2%至22%；此类细胞中分别有5%至42%和1%至45%弱表达CD20和CD37，且始终缺乏CD13和CD33。在4个样本中可见少量（0.1%至0.3%）细胞质μ+ sIg-前B细胞，其余4个样本中未检测到。因此，在所研究的8个样本中有5个样本的TdT+/cμ+比值大于100，而正常个体中该比值小于10。通过使用Ki67和抗溴脱氧尿苷单克隆抗体研究B淋巴细胞系祖细胞的增殖活性。尽管XLA中TdT+细胞的增殖与正常BM样本中的增殖相当（24%至59%的TdT+细胞为Ki67+，11%至27%的细胞掺入溴脱氧尿苷），但在cμ+细胞中增殖显著降低（在观察到前B细胞的3个样本中未见cμ+、Ki67+细胞）。因此，XLA中B细胞分化异常首先出现在cμ+前B阶段，提示在TdT+、cμ-前前B细胞和cμ+前B细胞之间的转变存在成熟阻滞。这种阻滞的严重程度可能各不相同，使得一些患者能够产生数量接近正常的前B细胞，但其增殖活性存在缺陷。最后，我们的研究通过证明XLA中携带TCR-αβ和TCR-γδ的T细胞比例与正常个体相似，进一步支持了“XLA基因”的作用局限于B淋巴细胞系这一概念。
