Bone morphogenetic proteins inhibit CD40L/IL-21-induced Ig production in human Bcells: Differential effects of BMP-6 and BMP-7

Authors

  • Kanutte Huse,

    1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
    2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Maren Bakkebø,

    1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
    2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Morten P. Oksvold,

    1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
    2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Lise Forfang,

    1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
    2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Vera I. Hilden,

    1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
    2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Trond Stokke,

    1. Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
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  • Erlend B. Smeland,

    1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
    2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • June H. Myklebust

    Corresponding author
    1. Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
    2. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
    • Department of Immunology, Institute for Cancer Research, Oslo University Hospital HF, The Norwegian Radium Hospital, Postboks 4953 Nydalen, 0424 Oslo, NorwayFax: +47-22-78-1445
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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.

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