Kneitz C, Goller M, Wilhelm M, Mehringer C, Wohlleben G, Schimpl A, Tony H P
Medizinische Poliklinik der Universität Würzburg, Germany.
Leukemia. 1999 Jan;13(1):98-104. doi: 10.1038/sj.leu.2401235.
The course of disease in patients suffering from chronic lymphocytic leukemia (CLL) is determined by a profound dysregulation of the immune system. The resulting immune suppression is the main cause of death in those patients. In the present study we addressed the question of whether leukemic B cells (B-CLL) are able to suppress regular T cell/B cell interaction. Activated CD4+ T cell clones induce expression of the early activation antigen CD23 on B lymphocytes in vitro. Under conditions used, this B cell activation event was dependent upon direct T cell contact. Addition of certain bystander B-CLL cells or normal B lymphocytes resulted in a cell number-dependent inhibition of B cell induction. This seems to reflect the competition of B-CLL cells for a cell contact-mediated T cell helper signal. By using CD40 ligand transfected fibroblasts as a substitute for T cell help, we show that the same B-CLL cells also suppress CD40 ligand-mediated B cell activation. B-CLL cells differ in their ability to inhibit CD40 ligand-mediated B cell activation. Some B-CLL cases (eight out of 14) are unable to compete for the T cell or CD40 ligand-mediated signal, even though they can functionally interact with CD40 ligand and thereby get activated themselves. In addition, these results indicate that the observed inhibition is not a result of cell crowding by merely reducing the chance of specific B cell/T cell interactions. Collectively, these data indicate that B-CLL cells are able to inhibit the interaction of activated T lymphocytes with normal B lymphocytes in vitro. Perturbed T cell/B cell interaction may represent an important mechanism underlying the various defects of the specific immune system observed in patients suffering from B-CLL.
慢性淋巴细胞白血病（CLL）患者的病程由免疫系统的严重失调决定。由此产生的免疫抑制是这些患者死亡的主要原因。在本研究中，我们探讨了白血病B细胞（B-CLL）是否能够抑制正常T细胞/B细胞相互作用的问题。活化的CD4 + T细胞克隆在体外可诱导B淋巴细胞上早期活化抗原CD23的表达。在所使用的条件下，这种B细胞活化事件依赖于T细胞的直接接触。添加某些旁观者B-CLL细胞或正常B淋巴细胞会导致B细胞诱导的细胞数量依赖性抑制。这似乎反映了B-CLL细胞对细胞接触介导的T细胞辅助信号的竞争。通过使用转染了CD40配体的成纤维细胞作为T细胞辅助的替代物，我们表明相同的B-CLL细胞也抑制CD40配体介导的B细胞活化。B-CLL细胞在抑制CD40配体介导的B细胞活化的能力上存在差异。一些B-CLL病例（14例中的8例）无法竞争T细胞或CD40配体介导的信号，即使它们能够与CD40配体进行功能相互作用并因此自身被激活。此外，这些结果表明观察到的抑制不是仅仅通过减少特定B细胞/T细胞相互作用的机会而导致的细胞拥挤的结果。总体而言，这些数据表明B-CLL细胞在体外能够抑制活化的T淋巴细胞与正常B淋巴细胞的相互作用。T细胞/B细胞相互作用紊乱可能是B-CLL患者中观察到的特异性免疫系统各种缺陷的重要潜在机制。
