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

Michio M. Kawano, Keiichiro Mihara, Naihui Huang, Takako Tsujimoto, Atsushi Kuramoto

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)487-494
Number of pages8
JournalBlood
Volume85
Issue number2
DOIs
Publication statusPublished - 15-01-1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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