{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:17:41Z","timestamp":1792811861339,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,3,3]],"date-time":"2010-03-03T00:00:00Z","timestamp":1267574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BE2813\/1-1"],"award-info":[{"award-number":["BE2813\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>PI3K isoforms p110\u03b3 and p110\u03b4 are required for early B cell development, peripheral maintenance, transformation by the Abelson oncogene, and LPS-induced proliferation.<\/jats:p>\n               <jats:p>Class I PI3K-dependent signaling regulates cell proliferation, differentiation, and survival. Analysis of gene-deficient mice revealed specific roles for the hematopoietically expressed PI3K catalytic subunits, p110\u03b3 and p110\u03b4, in development and function of T and B lymphocytes. However, the functional redundancy between these two PI3K isoforms in the B cell lineage remains unclear. Here, we demonstrate that p110\u03b4 and p110\u03b3 are expressed in B cells at early developmental stages. Normal B cell differentiation requires both isoforms, as p110\u03b3\/p110\u03b4 double deficiency causes an increased percentage of CD43hi\/B220+\/CD19\u2212 cells as compared with single deficiency. Interestingly, initial transformation efficiency of B cell precursors was strongly reduced in double-deficient cells following transformation by p185 bcr-abl or v-abl oncogenes as compared with single-deficient cells. The requirement of p110\u03b3 and p110\u03b4 in B cell development is underlined by reduced splenic B cell numbers of p110\u03b3\/p110\u03b4 double-deficient mice and of lethally irradiated wild-type mice reconstituted with double-deficient BM. Moreover, the peripheral maintenance of p110\u03b3\/p110\u03b4 double-deficient T and B cells was highly impaired following adoptive transfer of double-deficient splenocytes into wild-type mice. Functionally, LPS stimulation of splenocytes revealed proliferation defects resulting in decreased survival of p110\u03b3\/p110\u03b4 double-deficient B cells, which correlated with impaired induction of D-type cyclins and Bcl-XL. Surprisingly, this was not observed when purified B cells were analyzed, indicating a contribution of likely cell-extrinsic factor(s) to the impaired proliferation of double-deficient B cells. Thus, we provide novel evidence that p110\u03b3 and p110\u03b4 have overlapping and cell-extrinsic roles in the development, peripheral maintenance, and function of B cells.<\/jats:p>","DOI":"10.1189\/jlb.0809585","type":"journal-article","created":{"date-parts":[[2010,3,4]],"date-time":"2010-03-04T03:54:26Z","timestamp":1267674866000},"page":"1083-1095","source":"Crossref","is-referenced-by-count":58,"title":["The catalytic PI3K isoforms p110\u03b3 and p110\u03b4 contribute to B cell development and maintenance, transformation, and proliferation"],"prefix":"10.1093","volume":"87","author":[{"given":"Sandra","family":"Beer-Hammer","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"},{"name":"Institut f\u00fcr Experimentelle und Klinische Pharmakologie und Toxikologie und Interfakult\u00e4res Zentrum f\u00fcr Pharmakogenomik und Arzneimittelforschung (ICePhA), Klinikum der Eberhard-Karls-Universit\u00e4t T\u00fcbingen , T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Zebedin","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmakologie, Zentrum f\u00fcr Biomolekulare Medizin, Medizinische Universit\u00e4t Wien , Wien, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"von Holleben","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Alferink","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Psychiatrie, Life and Brain Center, Universit\u00e4t Bonn , Bonn, Germany"},{"name":"Klinik und Poliklinik f\u00fcr Psychiatrie und Psychotherapie, Universit\u00e4tsklinikum Bonn , Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Reis","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Dresing","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Degrandi","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Scheu","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Genetics, Biology and Biochemistry, University of Torino , Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Sexl","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmakologie, Zentrum f\u00fcr Biomolekulare Medizin, Medizinische Universit\u00e4t Wien , Wien, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle und Klinische Pharmakologie und Toxikologie und Interfakult\u00e4res Zentrum f\u00fcr Pharmakogenomik und Arzneimittelforschung (ICePhA), Klinikum der Eberhard-Karls-Universit\u00e4t T\u00fcbingen , T\u00fcbingen, Germany"},{"name":"Biochemie und Molekularbiologie II, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland P","family":"Piekorz","sequence":"additional","affiliation":[{"name":"Biochemie und Molekularbiologie II, Universit\u00e4tsklinikum der Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf , D\u00fcsseldorf, 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