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(Journal of Leukocyte Biology. 2002;71:987-995.)
© 2002 by Society for Leukocyte Biology

Bone marrow CD34+ progenitor cells stimulated with stem cell factor and GM-CSF have the capacity to activate IgD- B cells through direct cellular interaction

Shunsei Hirohata*, Tamiko Yanagida*, Tetsuya Tomita{dagger}, Hideki Yoshikawa{dagger} and Takahiro Ochi{dagger}

* Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan; and
{dagger} Department of Orthopedic Surgery, Osaka University Medical School, Japan

Correspondence: Shunsei Hirohata, M.D., Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. E-mail: shunsei{at}med.teikyo-u.ac.jp

Recent studies have suggested the involvement of bone marrow in the pathogenesis of rheumatoid arthritis (RA), in which proliferation of monocyte-lineage cells (MLC) as well as local B cell activation in the synovium play an important role. Here, we show that bone marrow-derived MLC have the capacity to activate human peripheral blood IgD- B cells. Bone marrow CD34+ cells from RA patients that had been stimulated with stem cell factor and GM-CSF for 3–4 weeks (>90% CD14+ HLA-DR+ cells, <0.5% CD19+ B cells, and <0.5% CD3+ T cells; MLC) induced the production of IgG much more effectively than that of IgM by highly purified B cells from healthy donors in the presence of IL-2 and IL-10. CD34+ cells from cord blood or from bone marrow of osteoarthritis patients also displayed the capacity to induce IgG production. The induction of IgG production by the bone marrow-derived MLC was markedly decreased when they were separated from B cells by a membrane filter. The bone marrow-derived MLC interacted preferentially with IgD- B cells to induce IgG production. These results indicate that upon stimulation with stem cell factor and GM-CSF, CD34+ progenitor cells differentiate into MLC that activate preferentially IgD- B cells through direct cellular interactions to produce IgG. Therefore, the data suggest that the accelerated recruitment of MLC from the bone marrow to the synovium might play a role in the local B cell activation in RA.

Key Words: human • B lymphocytes • cell-to-cell interactions




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