{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:16:49Z","timestamp":1792023409595,"version":"4.4.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Signal transduction from the BCR is regulated by the equilibrium between kinases (e.g., spleen tyrosine kinase [Syk]) and phosphatases (e.g., Shp-1). Previous studies showed that Syk-deficient B cells have a developmental block at the pro\/pre\u2013B cell stage, whereas a B cell\u2013specific Shp-1 deficiency promoted B-1a cell development and led to autoimmunity. We generated B cell\u2013specific Shp-1 and Syk double-knockout (DKO) mice and compared them to the single-knockout mice deficient for either Syk or Shp-1. Unlike Syk-deficient mice, the DKO mice can generate mature B cells, albeit at &amp;gt;20-fold reduced B cell numbers. The DKO B-2 cells are all Syk-negative, whereas the peritoneal B1 cells of the DKO mice still express Syk, indicating that they require this kinase for their proper development. The DKO B-2 cells cannot be stimulated via the BCR, whereas they are efficiently activated via TLR or CD40. We also found that in DKO pre-B cells, the kinase Zap70 is associated with the pre-BCR, suggesting that Zap70 is important to promote B cell maturation in the absence of Syk and SHP-1. Together, our data show that a properly balanced kinase\/phosphatase equilibrium is crucial for normal B cell development and function.<\/jats:p>","DOI":"10.4049\/jimmunol.1203040","type":"journal-article","created":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T03:12:25Z","timestamp":1401937945000},"page":"268-276","source":"Crossref","is-referenced-by-count":37,"title":["The Role of the Syk\/Shp-1 Kinase-Phosphatase Equilibrium in B Cell Development and Signaling"],"prefix":"10.1093","volume":"193","author":[{"given":"Ameera","family":"Alsadeq","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology, Max-Planck-Institut of Immunobiology and Epigenetics , Freiburg 79108 ,","place":["Germany"]},{"name":"Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]},{"name":"Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Hobeika","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Max-Planck-Institut of Immunobiology and Epigenetics , Freiburg 79108 ,","place":["Germany"]},{"name":"Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Medgyesi","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Max-Planck-Institut of Immunobiology and Epigenetics , Freiburg 79108 ,","place":["Germany"]},{"name":"Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Kl\u00e4sener","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Max-Planck-Institut of Immunobiology and Epigenetics , Freiburg 79108 ,","place":["Germany"]},{"name":"Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Reth","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Max-Planck-Institut of Immunobiology and Epigenetics , Freiburg 79108 ,","place":["Germany"]},{"name":"Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]},{"name":"Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg , Freiburg 79108 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,7,1]]},"reference":[{"key":"2025030707193593700_r1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev.immunol.18.1.495","article-title":"The RAG proteins and V(D)J recombination: complexes, ends, and transposition","volume":"18","author":"Fugmann","year":"2000","journal-title":"Annu. 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