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Publication : The serine/threonine phosphatase PP4 is required for pro-B cell development through its promotion of immunoglobulin VDJ recombination.

First Author  Su YW Year  2013
Journal  PLoS One Volume  8
Issue  7 Pages  e68804
PubMed ID  23874770 Mgi Jnum  J:204399
Mgi Id  MGI:5532450 Doi  10.1371/journal.pone.0068804
Citation  Su YW, et al. (2013) The serine/threonine phosphatase PP4 is required for pro-B cell development through its promotion of immunoglobulin VDJ recombination. PLoS One 8(7):e68804
abstractText  PP4 phosphatase regulates a number of crucial processes but the role of PP4 in B cells has never been reported. We generated B cell-specific pp4 knockout mice and have identified an essential role for PP4 in B cell development. Deficiency of PP4 in B lineage cells leads to a strong reduction in pre-B cell numbers, an absence in immature B cells, and a complete loss of mature B cells. In PP4-deficient pro-B cells, immunoglobulin (Ig) DJ(H) recombination is impaired and Ig micro heavy chain expression is greatly decreased. In addition, PP4-deficient pro-B cells show an increase of DNA double-strand breaks at Ig loci. Consistent with their reduced numbers, residual PP4-deficient pre-B cells accumulate in the G1 phase, exhibit excessive DNA damage, and undergo increased apoptosis. Overexpression of transgenic Ig in PP4-deficient mice rescues the defect in B cell development such that the animals have normal numbers of IgM(+) B cells. Our study therefore reveals a novel function for PP4 in pro-B cell development through its promotion of V(H)DJ(H) recombination.
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