Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development
Abstract Mice lacking secreted IgM (sIgM −/−) antibodies display abnormal splenic B cell development, which results in increased marginal zone and decreased follicular B cell numbers. However, the mechanism by which sIgM exhibit this effect is unknown. Here, we demonstrate that B cells in sIgM −/− m...
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Nature Portfolio
2017
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oai:doaj.org-article:3895420cee06482aa60c257f0ce6ddf62021-12-02T11:53:03ZSecreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development10.1038/s41598-017-03688-82045-2322https://doaj.org/article/3895420cee06482aa60c257f0ce6ddf62017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03688-8https://doaj.org/toc/2045-2322Abstract Mice lacking secreted IgM (sIgM −/−) antibodies display abnormal splenic B cell development, which results in increased marginal zone and decreased follicular B cell numbers. However, the mechanism by which sIgM exhibit this effect is unknown. Here, we demonstrate that B cells in sIgM −/− mice display increased B cell receptor (BCR) signaling as judged by increased levels of phosphorylated Bruton’s tyrosine kinase (pBtk), phosphorylated Spleen tyrosine kinase (pSyk), and nuclear receptor Nur77. Low dosage treatment with the pBtk inhibitor Ibrutinib reversed the altered B cell development in the spleen of sIgM −/− mice, suggesting that sIgM regulate splenic B cell differentiation by decreasing BCR signaling. Mechanistically, we show that B cells, which express BCRs specific to hen egg lysozyme (HEL) display diminished responsiveness to HEL stimulation in presence of soluble anti-HEL IgM antibodies. Our data identify sIgM as negative regulators of BCR signaling and suggest that they can act as decoy receptors for self-antigens that are recognized by membrane bound BCRs.Dimitrios TsiantoulasMate KissBarbara Bartolini-GrittiAndreas BergthalerZiad MallatHassan JumaaChristoph J. BinderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Dimitrios Tsiantoulas Mate Kiss Barbara Bartolini-Gritti Andreas Bergthaler Ziad Mallat Hassan Jumaa Christoph J. Binder Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development |
| description |
Abstract Mice lacking secreted IgM (sIgM −/−) antibodies display abnormal splenic B cell development, which results in increased marginal zone and decreased follicular B cell numbers. However, the mechanism by which sIgM exhibit this effect is unknown. Here, we demonstrate that B cells in sIgM −/− mice display increased B cell receptor (BCR) signaling as judged by increased levels of phosphorylated Bruton’s tyrosine kinase (pBtk), phosphorylated Spleen tyrosine kinase (pSyk), and nuclear receptor Nur77. Low dosage treatment with the pBtk inhibitor Ibrutinib reversed the altered B cell development in the spleen of sIgM −/− mice, suggesting that sIgM regulate splenic B cell differentiation by decreasing BCR signaling. Mechanistically, we show that B cells, which express BCRs specific to hen egg lysozyme (HEL) display diminished responsiveness to HEL stimulation in presence of soluble anti-HEL IgM antibodies. Our data identify sIgM as negative regulators of BCR signaling and suggest that they can act as decoy receptors for self-antigens that are recognized by membrane bound BCRs. |
| format |
article |
| author |
Dimitrios Tsiantoulas Mate Kiss Barbara Bartolini-Gritti Andreas Bergthaler Ziad Mallat Hassan Jumaa Christoph J. Binder |
| author_facet |
Dimitrios Tsiantoulas Mate Kiss Barbara Bartolini-Gritti Andreas Bergthaler Ziad Mallat Hassan Jumaa Christoph J. Binder |
| author_sort |
Dimitrios Tsiantoulas |
| title |
Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development |
| title_short |
Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development |
| title_full |
Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development |
| title_fullStr |
Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development |
| title_full_unstemmed |
Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development |
| title_sort |
secreted igm deficiency leads to increased bcr signaling that results in abnormal splenic b cell development |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/3895420cee06482aa60c257f0ce6ddf6 |
| work_keys_str_mv |
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1718394860752338944 |