Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis

• Published in: Blood Vol. 85; no. 2; pp. 487 - 494
• Main Authors: Kawano, MM, Mihara, K, Huang, N, Tsujimoto, T, Kuramoto, A
• Format: Journal Article
• Language: English
• Published: 15.01.1995
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V85.2.487.bloodjournal852487

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.