Huang N, Kawano M M, Mahmoud M S, Mihara K, Tsujimoto T, Niwa O, Kuramoto A
Department of Hematology and Oncology, Hiroshima University, Japan.
Blood. 1995 Jun 15;85(12):3704-12.
The mature myeloma cells express very late antigen 5 (VLA-5) and MPC-1 antigens on their surface and adhere to bone marrow (BM) stromal cells more tightly than the VLA-5-MPC-1- immature myeloma cells in vitro. The VLA-5 and MPC-1 antigens possibly function as two of the molecules responsible for interaction of mature myeloma cells with BM stromal cells. However, the immature myeloma cells do interact with BM stromal cells, and it is unclear which adhesion molecules mediate their interaction. In this study, we found that both immature and mature myeloma cells expressed CD21, an adhesion molecule known to bind to CD23. CD21 was also detected on normal plasma cells. To evaluate the role of CD21 expression on myeloma cells, two myeloma cell lines, NOP-2 (VLA-5-MPC-1-) and KMS-5 (VLA-5+MPC-1+), were used as representatives of immature and mature myeloma cell types, respectively, and an adhesion assay was performed between the myeloma cell lines and BM stromal cells. Antibody-blocking results showed that adhesion of the mature type KMS-5 to KM102, a human BM-derived stromal cell line, or to short-term cultured BM primary stromal cells was inhibited by monoclonal antibodies (MoAbs) against CD21, VLA-5, and MPC-1, and inhibition of adhesion of the immature type NOP-2 to KM102 by the anti-CD21 MoAb was observed as well. Furthermore, CD23 was detected on KM102. Treatment of KM102 with an anti-CD23 MoAb also inhibited adhesion of either KMS-5 or NOP-2 to KM102. Therefore, we propose that CD21 expressed on myeloma cells likely functions as a molecule responsible for the interaction of immature myeloma cells as well as mature myeloma cells with BM stromal cells, and CD23 may be the ligand on the stromal cells for the CD21-mediated adhesion.
成熟骨髓瘤细胞在其表面表达极晚期抗原5(VLA-5)和MPC-1抗原,并且在体外比VLA-5-MPC-1-未成熟骨髓瘤细胞更紧密地黏附于骨髓(BM)基质细胞。VLA-5和MPC-1抗原可能是负责成熟骨髓瘤细胞与BM基质细胞相互作用的两种分子。然而,未成熟骨髓瘤细胞确实与BM基质细胞相互作用,尚不清楚哪些黏附分子介导它们的相互作用。在本研究中,我们发现未成熟和成熟骨髓瘤细胞均表达CD21,一种已知可与CD23结合的黏附分子。在正常浆细胞上也检测到了CD21。为了评估CD21在骨髓瘤细胞上表达的作用,分别使用两种骨髓瘤细胞系NOP-2(VLA-5-MPC-1-)和KMS-5(VLA-5+MPC-1+)作为未成熟和成熟骨髓瘤细胞类型的代表,并在骨髓瘤细胞系与BM基质细胞之间进行黏附试验。抗体阻断结果显示,抗CD21、VLA-5和MPC-1的单克隆抗体(MoAbs)抑制了成熟型KMS-5与人类BM来源的基质细胞系KM102或短期培养的BM原代基质细胞的黏附,并且也观察到抗CD21 MoAb抑制未成熟型NOP-2与KM102的黏附。此外,在KM102上检测到了CD23。用抗CD23 MoAb处理KM102也抑制了KMS-5或NOP-2与KM102的黏附。因此,我们提出骨髓瘤细胞上表达的CD21可能是负责未成熟骨髓瘤细胞以及成熟骨髓瘤细胞与BM基质细胞相互作用的分子,并且CD23可能是基质细胞上CD21介导黏附的配体。