A novel stromal cell-dependent B lymphoid stem-like cell line that induces immunoglobulin gene rearrangement

Ken Ichi Matsuda, Masahito Koguma, Ryuhei Okuyama, Tomoko Nakazawa, Yumi Matsuzaki, Hiromitsu Nakauchi, Nobuaki Yanai, Tetsuya Terasaki, Masuo Obinata

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

A stroma-dependent B lymphoid cell line (B31-1) has been established by coculturing sorted stem cells on a novel bone marrow stromal cell line (TBR31-1). B31-1 cells express B220, but do not express other B lymphoid differentiation markers including CD43, heat stable antigen (HSA), or surface immunoglobulin (Ig)M (sIgM), and their Ig heavy chain (IgH) gene loci are germ-line in configuration. The addition of interleukin (IL)-7 or coculture with another stromal cell line, ST2, induces D-J rearrangement of the IgH gene and B lymphocyte differentiation markers. B31-1 cells restore an in vivo repopulation activity to lethally irradiated mice, and the repopulated cells differentiate to HSA+ pre-B cells. Continuous coculture results in two distinct populations, B220- c-Kit+ cells and B220+ c-Kit+ cells; B220- c-Kit+ cells are self-renewed and differentiate to B220+ c-Kit+ cells, while B220+ c-Kit+ cells produce only B220+ c-Kit+ cells. Both B220- and B220+ cells similarly express the IgH germ-line transcript (Iμ), mRNAs for recombinase (TdT, Rag-1, and Rag-2), and lymphoid-specific transcription factors (Pax-5, EBF, E12/E47, Oct-2, and Ikaros), but the DNA binding activity of Pax-5, EBF, Oct-2, and E2A are low in B220- cells and while high in B220+ cells. These results suggest the existence of at least two active states in the IgH locus before the induction of IgH gene rearrangement during B lymphopoietic development.

Original languageEnglish
Pages (from-to)602-612
Number of pages11
JournalJournal of biochemistry
Volume125
Issue number3
DOIs
Publication statusPublished - 1999 Jan 1

Keywords

  • B-cell differentiation
  • Early B-cell progenitor
  • Hematopoietic stem cell
  • Immunoglobulin gene rearrangement
  • Stromal cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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