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Differentiation of early plasma cells on bone marrow stromal cells requires
interleukin-6 for escaping from apoptosis
MM Kawano, K Mihara, N Huang, T Tsujimoto and A Kuramoto
Department of Hematology and Oncology, Hiroshima University, Japan.
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.
Volume 85,
Issue 2,
pp. 487-494,
01/15/1995
Copyright © 1995 by The American Society of Hematology
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