Open AccessAcute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway
Author(s) -
Wen Lu,
Katarzyna M. Skrzypczynska,
Arthur Weiss
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2108957118
Subject(s) - tyrosine protein kinase csk , microbiology and biotechnology , src family kinase , proto oncogene tyrosine protein kinase src , signal transduction , tyrosine kinase , kinase , t cell receptor , biology , mapk/erk pathway , chemistry , t cell , sh3 domain , immunology , immune system
Significance B lymphocytes recognize pathogenic antigens and become activated via their B cell receptors (BCR). This BCR-dependent activation is controlled by Src-family kinases (SFKs). It is unclear how B cells tolerate the fluctuations of SFK activities and maintain unresponsiveness in the absence of foreign antigens. Using a chemical-genetic system, we acutely inhibited C-terminal Src kinase to enhance the SFK activity in mouse B cells. Surprisingly, we observed marked inhibition of BCR-downstream signaling due to associated impairment of the phosphatidylinositol-trisphosphate pathway. These results reveal the critical importance of maintaining a proper amount of SFK activity in quiescent B cells for appropriate BCR-dependent responses, which may be critical for naïve B cell unresponsiveness to self-antigens to maintain peripheral tolerance.