BAFF and APRIL regulate B cell homeostasis by binding to their three receptors BAFFR, BCMA and TACI. The complexity of this system is further increased by shedding of these three receptors; this reduces signaling due to the display of less surface receptors. Further, soluble forms, sBCMA and sTACI, were detected in body fluids and serve as biomarker in malignancies, autoimmune diseases and immunodeficiencies. sBCMA and sTACI function as decoys blocking BAFF and APRIL. BCMA is a promising therapeutic target in multiple myeloma, but sBCMA may reduce therapeutic activity of CAR T cells, bispecific antibodies, and antibody-drug conjugates. Insights into the biochemical mechanism of shedding of BCMA can be harnessed to improve BCMA-directed therapy by blocking its shedding with a γ-secretase inhibitor.

中文翻译：

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内源性可溶性受体 sBCMA 和 sTACI：多发性骨髓瘤治疗的生物标志物、免疫调节剂和障碍。

BAFF 和 APRIL 通过与其三种受体 BAFFR、BCMA 和 TACI 结合来调节 B 细胞稳态。这三个受体的脱落进一步增加了这个系统的复杂性；由于显示较少的表面受体，这减少了信号传导。此外，在体液中检测到可溶形式 sBCMA 和 sTACI，它们可作为恶性肿瘤、自身免疫性疾病和免疫缺陷的生物标志物。sBCMA 和 sTACI 用作阻止 BAFF 和 APRIL 的诱饵。BCMA 是多发性骨髓瘤的一个有希望的治疗靶点，但 sBCMA 可能会降低 CAR T 细胞、双特异性抗体和抗体-药物偶联物的治疗活性。对 BCMA 脱落的生化机制的了解可用于通过用 γ-分泌酶抑制剂阻断其脱落来改善 BCMA 定向治疗。