title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. shunsei@med.teikyo-u.ac.jp
authors.forename: Shunsei
authors.initials: S
authors.lastname: Hirohata
authors.forename: Tamiko
authors.initials: T
authors.lastname: Yanagida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tomita
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochi
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000601:surgery; D019644:Arthroplasty, Replacement, Hip; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis*; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D012016:Reference Values; D019089:Stem Cell Factor / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D007072:Immunoglobulin D; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor