Moore J S, Prystowsky M B, Hoover R G, Besa E C, Nowell P C
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Blood. 1988 Apr;71(4):1012-20.
The consistent occurrence of T cell abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that the non-neoplastic host T cells may be involved in the pathogenesis of this B cell neoplasm. Because potential defects of immunoglobulin regulation are evident in B-CLL patients, we investigated one aspect of this by studying the T cell-mediated immunoglobulin isotype-specific immunoregulatory circuit in B-CLL. The existence of class-specific immunoglobulin regulatory mechanisms mediated by Fc receptor-bearing T cells (FcR + T) through soluble immunoglobulin binding factors (IgBFs) has been well established in many experimental systems. IgBFs can both suppress and enhance B cell activity in an isotype-specific manner. We investigated the apparently abnormal IgA regulation in a B-CLL patient (CLL249) whose B cells secrete primarily IgA in vitro. Enumeration of FcR + T cells showed a disproportionate increase in IgA FcR + T cells in the peripheral blood of this patient. Our studies showed that the neoplastic B cells were not intrinsically unresponsive to the suppressing component of IgABF produced from normal T cells, but rather the IgABF produced by the CLL249 host T cells was defective. CLL249 IgABF was unable to suppress IgA secretion by host or normal B cells and enhanced the in vitro proliferation of the host B cells. Size fractionation of both normal and CLL249 IgABF by gel-filtration high-performance liquid chromatography (HPLC) demonstrated differences in the ultraviolet-absorbing components of IgABF obtained from normal T cells v that from our patient with defective IgA regulation. Such T cell dysfunction may not be restricted to IgA regulation, since we have found similar expansion of isotype-specific FcR + T cells associated with expansion of the corresponding B cell clone in other patients with B-CLL. These data suggest that this T cell-mediated regulatory circuit could be significantly involved in the pathogenesis of B-CLL.
B细胞慢性淋巴细胞白血病（B-CLL）患者中持续出现T细胞异常，这表明非肿瘤性宿主T细胞可能参与了这种B细胞肿瘤的发病机制。由于B-CLL患者中免疫球蛋白调节的潜在缺陷很明显，我们通过研究B-CLL中T细胞介导的免疫球蛋白同种型特异性免疫调节回路来探究这一方面。在许多实验系统中，由携带Fc受体的T细胞（FcR + T）通过可溶性免疫球蛋白结合因子（IgBFs）介导的类别特异性免疫球蛋白调节机制已得到充分证实。IgBFs可以以同种型特异性方式抑制和增强B细胞活性。我们研究了一名B-CLL患者（CLL249）中明显异常的IgA调节，该患者的B细胞在体外主要分泌IgA。FcR + T细胞计数显示该患者外周血中IgA FcR + T细胞不成比例地增加。我们的研究表明，肿瘤性B细胞并非本质上对正常T细胞产生的IgABF的抑制成分无反应，而是CLL249宿主T细胞产生的IgABF存在缺陷。CLL249 IgABF无法抑制宿主或正常B细胞的IgA分泌，并增强了宿主B细胞的体外增殖。通过凝胶过滤高效液相色谱（HPLC）对正常和CLL249 IgABF进行大小分级，结果表明从正常T细胞获得的IgABF与来自我们患有IgA调节缺陷患者的IgABF在紫外线吸收成分上存在差异。这种T细胞功能障碍可能不限于IgA调节，因为我们在其他B-CLL患者中发现了同种型特异性FcR + T细胞的类似扩增，且与相应B细胞克隆的扩增相关。这些数据表明，这种T细胞介导的调节回路可能在B-CLL的发病机制中起重要作用。
