{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T01:58:22Z","timestamp":1767923902715,"version":"3.49.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"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":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ligand-engaged chemoattractant receptors trigger G\u03b1i subunit nucleotide exchange, stimulating the activation of downstream effector molecules. Activated chemoattractant receptors also dock G protein\u2013coupled receptor kinases (GRKs) that help mediate receptor desensitization. In this study, we show that the B cell\u2013specific loss of GRK2 severely disrupts B cell trafficking and immune cell homeostasis. The GRK2 deficiency in developing murine B cells leads to a severe immune phenotype, including a major reduction of bone marrow IgD+ cells, splenomegaly with a loss of white pulp and grossly expanded red pulp, a deficit of Peyer patches, and small lymph nodes with marked reductions in B cell numbers. The major phenotypes in these mice arise from excessive S1PR1 signaling combined with inadequate homeostatic chemokine receptor signaling. CXCL13 signaling is the most severely compromised. In B cells, our data also indicate that S1PR1 signals constitutively, as blocking S1PR1 signaling with an S1PR1 antagonist enhanced CXCL13-triggered wild-type B cell migration. Furthermore, blocking S1PR1 signaling in the GRK2-deficient B cells partially corrected their poor response to chemokines. Treating mice lacking GRK2 expression in their B cells with an S1PR1 antagonist partially normalized B cell trafficking into lymph node and splenic follicles. These findings reveal the critical interdependence of G\u03b1i-linked signaling pathways in controlling B lymphocyte trafficking.<\/jats:p>","DOI":"10.4049\/jimmunol.1900678","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T18:35:18Z","timestamp":1569263718000},"page":"2401-2414","source":"Crossref","is-referenced-by-count":13,"title":["Biased S1PR1 Signaling in B Cells Subverts Responses to Homeostatic Chemokines, Severely Disorganizing Lymphoid Organ Architecture"],"prefix":"10.1093","volume":"203","author":[{"given":"Il-Young","family":"Hwang","sequence":"first","affiliation":[{"name":"B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7819-5333","authenticated-orcid":false,"given":"Chung","family":"Park","sequence":"additional","affiliation":[{"name":"B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Harrison","sequence":"additional","affiliation":[{"name":"B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-159X","authenticated-orcid":false,"given":"John H","family":"Kehrl","sequence":"additional","affiliation":[{"name":"B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,1]]},"reference":[{"key":"2025030417543761700_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ceb.2015.05.003","article-title":"Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses","volume":"36","author":"Lian","year":"2015","journal-title":"Curr. 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