In chronic lymphocytic leukemia (CLL), the B cell receptor (BCR) plays a critical role in disease development and progression, as indicated by the therapeutic efficacy of drugs blocking BCR signaling. However, the mechanism(s) underlying BCR responsiveness are not completely defined. Selective engagement of membrane IgM or IgD on CLL cells, each coexpressed by more than 90% of cases, leads to distinct signaling events. Since both IgM and IgD carry the same antigen-binding domains, the divergent actions of the receptors are attributed to differences in immunoglobulin (Ig) structure or the outcome of signal transduction. We showed that IgM, not IgD, level and organization associated with CLL-cell birth rate and the type and consequences of BCR signaling in humans and mice. The latter IgM-driven effects were abrogated when BCR signaling was inhibited. Collectively, these studies demonstrated a critical, selective role for IgM in BCR signaling and B cell fate decisions, possibly opening new avenues for CLL therapy.

中文翻译：

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B 细胞受体同种型与慢性淋巴细胞白血病的细胞信号传导、动力学和结果存在差异

在慢性淋巴细胞白血病 (CLL) 中，B 细胞受体 (BCR) 在疾病发展和进展中起关键作用，正如阻断 BCR 信号传导的药物的治疗效果所示。但是，BCR 响应性的机制尚未完全定义。膜 IgM 或 IgD 对 CLL 细胞的选择性参与，每个都由超过 90% 的病例共表达，导致不同的信号事件。由于 IgM 和 IgD 都携带相同的抗原结合结构域，因此受体的不同作用归因于免疫球蛋白 (Ig) 结构或信号转导结果的差异。我们展示了与 CLL 细胞出生率以及 BCR 信号在人类和小鼠中的类型和后果相关的 IgM 水平和组织，而不是 IgD。当 BCR 信号被抑制时，后一种 IgM 驱动的效应被消除。