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 ^-/- 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 expre

SUBMITTER: Tsiantoulas D 

PROVIDER: S-EPMC5471202 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature