Kawano M M, Mihara K, Huang N, Tsujimoto T, Kuramoto A
Department of Hematology and Oncology, Hiroshima University, Japan.
Blood. 1995 Jan 15;85(2):487-94.
The bone marrow (BM) is well known to be the major site of Ig production in secondary immune responses; thus, the microenvironment of BM is considered to be essential for final differentiation of plasma cells. We identified in the peripheral blood (PB) early plasma cells (CD38++CD19+VLA-5-) committed to entering the BM. The sorted early plasma cells rapidly entered apoptosis in vitro, but these cells could survive and further differentiate into mature plasma cells (CD38 CD19+) just as BM plasma cells in the presence of a BM-derived stromal cell line (KM-102). Culture supernatants of KM-102 cell lines could also support survival of these cells, and antibody to interleukin-6 (IL-6) completely blocked the effect of these supernatants. Furthermore, recombinant IL-6, but not IL-1 or IL-3, could support their survival and their differentiation into mature plasma cells (CD38 CD19+VLA-5+) with expression of VLA-5 mRNA. Therefore, here is direct evidence that early plasma cells found in the PB differentiated into mature plasma cells with stromal cell-derived IL-6 in vitro; thus, BM stromal cells control the final checkpoint of plasma cell differentiation with secretion of IL-6 in the BM.
众所周知，骨髓（BM）是二次免疫应答中免疫球蛋白产生的主要部位；因此，骨髓微环境被认为是浆细胞最终分化所必需的。我们在外周血（PB）中鉴定出了致力于进入骨髓的早期浆细胞（CD38++CD19+VLA-5-）。分选得到的早期浆细胞在体外迅速进入凋亡状态，但在存在骨髓来源的基质细胞系（KM-102）的情况下，这些细胞能够存活并进一步分化为成熟浆细胞（CD38 CD19+），就如同骨髓浆细胞一样。KM-102细胞系的培养上清液也能够支持这些细胞的存活，并且抗白细胞介素-6（IL-6）抗体能够完全阻断这些上清液的作用。此外，重组IL-6，而非IL-1或IL-3，能够支持它们的存活以及它们分化为表达VLA-5 mRNA的成熟浆细胞（CD38 CD19+VLA-5+）。因此，有直接证据表明在外周血中发现的早期浆细胞在体外可通过基质细胞来源的IL-6分化为成熟浆细胞；所以，骨髓基质细胞通过在骨髓中分泌IL-6来控制浆细胞分化的最终关卡。
