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It functions as a guanine nucleotide exchange factor for G\u03b1i, G\u03b1q, and G\u03b112\/13 and as a molecular chaperone required for the initial association of nascent G\u03b1 subunits with cellular membranes in embryonic stem cell lines. To test its role in hematopoiesis and B lymphocytes specifically, we generated ric8fl\/flvav1-cre and ric8fl\/flmb1-cre mice. The major hematopoietic cell lineages developed in the ric8fl\/flvav1-cre mice, notwithstanding severe reduction in G\u03b1i2\/3, G\u03b1q, and G\u03b113 proteins. B lymphocyte\u2013specific loss of Ric-8A did not compromise bone marrow B lymphopoiesis, but splenic marginal zone B cell development failed, and B cells underpopulated lymphoid organs. The ric8fl\/flmb1-cre B cells exhibited poor responses to chemokines, abnormal trafficking, improper in situ positioning, and loss of polarity components during B cell differentiation. The ric8fl\/flmb1-cre mice had a severely disrupted lymphoid architecture and poor primary and secondary Ab responses. In B lymphocytes, Ric-8A is essential for normal G\u03b1 protein levels and is required for B cell differentiation, trafficking, and Ab responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1500523","type":"journal-article","created":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T02:30:11Z","timestamp":1438396211000},"page":"2090-2102","source":"Crossref","is-referenced-by-count":20,"title":["B Lymphocyte\u2013Specific Loss of Ric-8A Results in a G\u03b1 Protein Deficit and Severe Humoral Immunodeficiency"],"prefix":"10.1093","volume":"195","author":[{"given":"Cedric","family":"Boularan","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"}]},{"given":"Il-Young","family":"Hwang","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":"Olena","family":"Kamenyeva","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":"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"}]},{"given":"Zhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Wisconsin\u2013Madison , Madison, WI 53706"},{"name":"Department of Neuroscience, University of Wisconsin\u2013Madison , Madison, WI 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[[2015,9,1]]},"reference":[{"key":"2025030704082563400_r1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S1877-1173(09)86009-2","article-title":"Regulation of immune function by G protein-coupled receptors, trimeric G proteins, and RGS proteins","volume":"86","author":"Cho","year":"2009","journal-title":"Prog. 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