| First Author | Gazumyan A | Year | 2006 |
| Journal | J Exp Med | Volume | 203 |
| Issue | 7 | Pages | 1785-94 |
| PubMed ID | 16818674 | Mgi Jnum | J:124400 |
| Mgi Id | MGI:3721472 | Doi | 10.1084/jem.20060221 |
| Citation | Gazumyan A, et al. (2006) Ig beta tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization. J Exp Med 203(7):1785-94 |
| abstractText | Immunoglobulin (Ig)alpha and Igbeta initiate B cell receptor (BCR) signaling through immune receptor tyrosine activation motifs (ITAMs) that are targets of SH2 domain-containing kinases. To examine the function of Igbeta ITAM tyrosine resides in mature B cells in vivo, we exchanged these residues for alanine by gene targeting (Igbeta(AA)). Mutant mice showed normal development of all B cell subtypes with the exception of B1 cells that were reduced by fivefold. However, primary B cells purified from Igbeta(AA) mice showed significantly decreased steady-state and ligand-mediated BCR internalization and higher levels of cell surface IgM and IgD. BCR cross-linking resulted in decreased Src and Syk activation but paradoxically enhanced and prolonged BCR signaling, as measured by cellular tyrosine phosphorylation, Ca(++) flux, AKT, and ERK activation. In addition, B cells with the ITAM mutant receptor showed an enhanced response to a T-independent antigen. Thus, Igbeta ITAM tyrosines help set BCR signaling threshold by regulating receptor internalization. |
