Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry.

Irish JM, Czerwinski DK, Nolan GP, Levy R
J Immunol. 2006 177 (3): 1581-9

PMID: 16849466 · DOI:10.4049/jimmunol.177.3.1581

Differences in BCR signaling may govern outcomes as diverse as proliferation and cell death. We profiled BCR signaling kinetics in subsets of primary human B cells using flow cytometry. In the predominant population expressing IgM, BCR cross-linking led to a quick burst of Syk, ERK1/2, and p38 signaling. In contrast, IgG B cells sustained higher per-cell ERK1/2 phosphorylation over time. This dichotomy suggested a mechanism for dampening signals transmitted by IgM. Regulatory phosphatase activity in IgM B cells was BCR-mediated and initiated more slowly than kinase activity. This BCR-mediated phosphatase activity was sensitive to inhibition by H(2)O(2) and required to attenuate IgM BCR signaling. These results provide the first kinetic maps of BCR signaling in primary human B cell subsets and enable new studies of signaling in B cell disorders, such as autoimmunity and cancer.

MeSH Terms (17)

Agammaglobulinaemia Tyrosine Kinase B-Lymphocyte Subsets Flow Cytometry Humans Hydrogen Peroxide Immunoglobulin G Immunoglobulin M Intracellular Signaling Peptides and Proteins Kinetics MAP Kinase Signaling System Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Peptide Mapping Phosphorylation Protein-Tyrosine Kinases Receptors, Antigen, B-Cell Syk Kinase

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