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Binding of HLA-G to ITIM-bearing Ig-like transcript 2 receptor suppresses B cell responses.
Naji, Abderrahim; Menier, Catherine; Morandi, Fabio; Agaugué, Sophie; Maki, Guitta; Ferretti, Elisa; Bruel, Sylvie; Pistoia, Vito; Carosella, Edgardo D; Rouas-Freiss, Nathalie.
Affiliation
  • Naji A; Commissariat à l'Energie Atomique et aux Énergies Alternatives, Institut des Maladies Emergentes et des Therapies Innovantes, Service de Recherche en Hemato-Immunologie, Hopital Saint-Louis, 75010 Paris, France;
J Immunol ; 192(4): 1536-46, 2014 Feb 15.
Article in En | MEDLINE | ID: mdl-24453251
Inhibition of B cells constitutes a rational approach for treating B cell-mediated disorders. We demonstrate in this article that the engagement of the surface Ig-like transcript 2 (ILT2) inhibitory receptor with its preferential ligand HLA-G is critical to inhibit B cell functions. Indeed, ILT2-HLA-G interaction impedes both naive and memory B cell functions in vitro and in vivo. Particularly, HLA-G inhibits B cell proliferation, differentiation, and Ig secretion in both T cell-dependent and -independent models of B cell activation. HLA-G mediates phenotypic and functional downregulation of CXCR4 and CXCR5 chemokine receptors on germinal center B cells. In-depth analysis of the molecular mechanisms mediated by ILT2-HLA-G interaction showed a G0/G1 cell cycle arrest through dephosphorylation of AKT, GSK-3ß, c-Raf, and Foxo proteins. Crucially, we provide in vivo evidence that HLA-G acts as a negative B cell regulator in modulating B cell Ab secretion in a xenograft mouse model. This B cell regulatory mechanism involving ILT2-HLA-G interaction brings important insight to design future B cell-targeted therapies aimed at reducing inappropriate immune reaction in allotransplantation and autoimmune diseases.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: B-Lymphocytes / Lymphocyte Activation / Receptors, Immunologic / Antigens, CD / HLA-G Antigens Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: J Immunol Year: 2014 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: B-Lymphocytes / Lymphocyte Activation / Receptors, Immunologic / Antigens, CD / HLA-G Antigens Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: J Immunol Year: 2014 Document type: Article Country of publication: United States