title: The serine/threonine phosphatase PP4 is required for pro-B cell development through its promotion of immunoglobulin VDJ recombination.
abstract: 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 µ 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.
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. yuwensu@nhri.org.tw
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Su
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.forename: Tse-Hua
authors.initials: TH
authors.lastname: Tan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded; D005434:Flow Cytometry; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4