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Bone morphogenetic proteins inhibit CD40L/IL‐21‐induced Ig production in human Bcells: Differential effects of BMP‐6 and BMP‐7
Author(s) -
Huse Kanutte,
Bakkebø Maren,
Oksvold Morten P.,
Forfang Lise,
Hilden Vera I.,
Stokke Trond,
Smeland Erlend B.,
Myklebust June H.
Publication year - 2011
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201141558
Subject(s) - bone morphogenetic protein , biology , downregulation and upregulation , bone morphogenetic protein 2 , bone morphogenetic protein 7 , bone morphogenetic protein 4 , cd40 , microbiology and biotechnology , bone morphogenetic protein 6 , transcription factor , bmpr2 , bone morphogenetic protein 5 , bone morphogenetic protein 8a , immunology , gene , genetics , in vitro , cytotoxic t cell
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.