Open AccessProliferation and Survival of Activated B Cells Requires Sustained Antigen Receptor Engagement and Phosphoinositide 3-Kinase Activation
Author(s) -
Amber C. Donahue,
David A. Fruman
Publication year - 2003
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.170.12.5851
Subject(s) - microbiology and biotechnology , intracellular , t cell receptor , receptor , biology , b cell receptor , cd28 , cell , t cell , signal transduction , cell growth , b cell , immunology , antibody , biochemistry , immune system
In this study, we investigate the extracellular and intracellular signals that drive cell cycle progression of activated B cells in the absence of T cell help. We find that brief engagement of the B cell receptor is sufficient to induce a single cell division in a fraction of cells, but that survival during successive cell divisions requires sustained receptor stimulation. In contrast, T cells have been shown previously to commit to multiple cell divisions following brief TCR engagement. Both early and late B cell receptor signals are blocked by inhibitors of phosphoinositide 3-kinase and mammalian target of rapamycin and are associated with S6 kinase activation and increased cell size. The requirement for ongoing Ag receptor signaling can be overcome by engagement of CD40 but only partially by IL-4. Proliferation driven by LPS also requires sustained exposure to the stimulus. These findings reveal checkpoints that may limit T-independent B cell responses when Ag exposure is transient.