title: The loss of Gnai2 and Gnai3 in B cells eliminates B lymphocyte compartments and leads to a hyper-IgM like syndrome.
abstract: B lymphocytes are compartmentalized within lymphoid organs. The organization of these compartments depends upon signaling initiated by G-protein linked chemoattractant receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in chemoattractant signaling we created mice lacking both proteins in their B lymphocytes. While bone marrow B cell development and egress is grossly intact; mucosal sites, splenic marginal zones, and lymph nodes essentially lack B cells. There is a partial block in splenic follicular B cell development and a 50-60% reduction in splenic B cells, yet normal numbers of splenic T cells. The absence of Gαi2 and Gαi3 in B cells profoundly disturbs the architecture of lymphoid organs with loss of B cell compartments in the spleen, thymus, lymph nodes, and gastrointestinal tract. This results in a severe disruption of B cell function and a hyper-IgM like syndrome. Beyond the pro-B cell stage, B cells are refractory to chemokine stimulation, and splenic B cells are poorly responsive to antigen receptor engagement. Gαi2 and Gαi3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function. These mice provide a worst case scenario of the consequences of losing chemoattractant receptor signaling in B cells.
authors: B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Il-Young
authors: IY
authors: Hwang
authors: Chung
authors: C
authors: Park
authors: Thuyvi
authors: T
authors: Luong
authors: Kathleen A
authors: KA
authors: Harrison
authors: Lutz
authors: L
authors: Birnbaumer
authors: John H
authors: JH
authors: Kehrl
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002451:Cell Compartmentation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology; D018450:Disease Progression; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000172:deficiency* / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000172:deficiency* / Q000378:metabolism; D018858:Germinal Center / Q000187:drug effects / Q000473:pathology; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology*; D007114:Immunization; D019426:Integrases / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000473:pathology
chemical_list: D018925:Chemokines; D002630:Chemotactic Factors; D016023:Integrins; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; C045073:Cre recombinase; D019426:Integrases; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse; C417708:Gnai3 protein, mouse
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