| First Author | Boularan C | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 5 | Pages | 2090-102 |
| PubMed ID | 26232433 | Mgi Jnum | J:302866 |
| Mgi Id | MGI:6510075 | Doi | 10.4049/jimmunol.1500523 |
| Citation | Boularan C, et al. (2015) B Lymphocyte-Specific Loss of Ric-8A Results in a Galpha Protein Deficit and Severe Humoral Immunodeficiency. J Immunol 195(5):2090-102 |
| abstractText | Resistance to inhibitors of cholinesterase 8A (Ric-8A) is a highly evolutionarily conserved cytosolic protein initially identified in Caenorhabditis elegans, where it was assigned a regulatory role in asymmetric cell divisions. It functions as a guanine nucleotide exchange factor for Galphai, Galphaq, and Galpha12/13 and as a molecular chaperone required for the initial association of nascent Galpha subunits with cellular membranes in embryonic stem cell lines. To test its role in hematopoiesis and B lymphocytes specifically, we generated ric8 (fl/fl) vav1-cre and ric8 (fl/fl) mb1-cre mice. The major hematopoietic cell lineages developed in the ric8 (fl/fl) vav1-cre mice, notwithstanding severe reduction in Galphai2/3, Galphaq, and Galpha13 proteins. B lymphocyte-specific 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 ric8 (fl/fl) mb1-cre B cells exhibited poor responses to chemokines, abnormal trafficking, improper in situ positioning, and loss of polarity components during B cell differentiation. The ric8 (fl/fl) mb1-cre mice had a severely disrupted lymphoid architecture and poor primary and secondary Ab responses. In B lymphocytes, Ric-8A is essential for normal Galpha protein levels and is required for B cell differentiation, trafficking, and Ab responses. |
