title: Bone morphogenetic proteins inhibit CD40L/IL-21-induced Ig production in human B cells: differential effects of BMP-6 and BMP-7.
abstract: Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily. TGF-β can affect class switch recombination in human B cells, but whether BMPs also play a role have not been tested. We investigated the functional effects of exogenously added BMPs on CD27(-)  naive and CD27(+)  memory B cells from healthy donors. BMP-2, -4, -6 and -7 inhibited CD40L/IL-21-induced production of IgM, IgG and IgA. BMP-6 reduced Ig production by 70% in memory B cells and more than 55% in naive B cells, whereas the other BMPs were slightly less potent. We observed a striking difference in functional effects between the structurally similar BMP-6 and BMP-7, as BMP-6 mainly inhibited plasmablast differentiation, and BMP-7 mainly induced apoptosis. In memory B cells, BMP-6 upregulated expression of DNA-binding protein inhibitor genes, but potently inhibited CD40L/IL-21-induced upregulation of the transcription factor XBP1, necessary for the late stages of plasmacytic differentiation. Expression of transcription factors regulating earlier stages (IRF4, PRDM1) was not affected by BMP-6. Taken together, these results show that BMPs are potent suppressors of naive and memory B cells.
authors: Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors: Kanutte
authors: K
authors: Huse
authors: Maren
authors: M
authors: Bakkebø
authors: Morten P
authors: MP
authors: Oksvold
authors: Lise
authors: L
authors: Forfang
authors: Vera I
authors: VI
authors: Hilden
authors: Trond
authors: T
authors: Stokke
authors: Erlend B
authors: EB
authors: Smeland
authors: June H
authors: JH
authors: Myklebust
mesh_terms: D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D055418:Bone Morphogenetic Protein 6 / Q000276:immunology*; D055419:Bone Morphogenetic Protein 7 / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000276:immunology; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D000098546:Interleukin-21
chemical_list: C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D007136:Immunoglobulins; D007378:Interleukins; D023201:CD40 Ligand; D000098546:Interleukin-21