TY - JOUR
T1 - Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis
AU - Kawano, Michio M.
AU - Mihara, Keiichiro
AU - Huang, Naihui
AU - Tsujimoto, Takako
AU - Kuramoto, Atsushi
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1995/1/15
Y1 - 1995/1/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.v85.2.487.bloodjournal852487
DO - 10.1182/blood.v85.2.487.bloodjournal852487
M3 - Article
C2 - 7812003
AN - SCOPUS:0028928641
SN - 0006-4971
VL - 85
SP - 487
EP - 494
JO - Blood
JF - Blood
IS - 2
ER -