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Grb2 regulates B‐cell maturation, B‐cell memory responses and inhibits B‐cell Ca 2+ signalling
Author(s) -
Ackermann Jochen A,
Radtke Daniel,
Maurberger Anna,
Winkler Thomas H,
Nitschke Lars
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.74
Subject(s) - biology , microbiology and biotechnology , cell , signalling , b cell , signal transduction , genetics , antibody
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.