| First Author | Ackermann JA | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 8 | Pages | 1621-33 |
| PubMed ID | 21427701 | Mgi Jnum | J:171222 |
| Mgi Id | MGI:4949011 | Doi | 10.1038/emboj.2011.74 |
| Citation | Ackermann JA, et al. (2011) Grb2 regulates B-cell maturation, B-cell memory responses and inhibits B-cell Ca(2+) signalling. EMBO J 30(8):1621-33 |
| abstractText | Grb2 is a ubiquitously expressed adaptor protein, which activates Ras and MAP kinases in growth factor receptor signalling, while in B-cell receptor (BCR) signalling this role is controversial. In B cell lines it was shown that Grb2 can inhibit BCR-induced Ca(2+) signalling. Nonetheless, the physiological role of Grb2 in primary B cells is still unknown. We generated a B-cell-specific Grb2-deficient mouse line, which had a severe reduction of mature follicular B cells in the periphery due to a differentiation block and decreased B-cell survival. Moreover, we found several changes in important signalling pathways: enhanced BCR-induced Ca(2+) signalling, alterations in mitogen-activated protein kinase activation patterns and strongly impaired Akt activation, the latter pointing towards a defect in PI3K signalling. Interestingly, B-cell-specific Grb2-deficient mice showed impaired IgG and B-cell memory responses, and impaired germinal centre formation. Thus, Grb2-dependent signalling pathways are crucial for lymphocyte differentiation processes, as well as for control of secondary humoral immune responses. |
