Open AccessSecreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development
Author(s) -
Dimitrios Tsiantoulas,
Máté G. Kiss,
Barbara Bartolini-Gritti,
Andréas Bergthaler,
Ziad Mallat,
Hassan Jumaa,
Christoph J. Binder
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-03688-8
Subject(s) - bruton's tyrosine kinase , breakpoint cluster region , b cell receptor , b cell , marginal zone , biology , spleen , receptor , signal transduction , antibody , cd38 , immunology , tyrosine kinase , microbiology and biotechnology , biochemistry , stem cell , cd34
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.