NCR1‐deficiency diminishes the generation of protective murine cytomegalovirus antibodies by limiting follicular helper T‐cell maturation. Issue 9 (21st July 2017)

• Record Type: Journal Article
• Authors: Miletic, Antonija; Lenartic, Maja; Popovic, Branka; Brizic, Ilija; Trsan, Tihana; Miklic, Karmela; Mandelboim, Ofer; Krmpotic, Astrid; Jonjic, Stipan
• Is Part Of: European journal of immunology. Volume 47:Issue 9(2017)
• Page Start: 1443
• Page End: 1456
• Publication Date: 2017-07-21
• Subjects: Antiviral antibodies -- Follicular helper T cells -- Germinal center B cells -- NCR1 receptor -- NK‐cell immunoregulation -- Viral infection; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646763
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : NCR1‐deficient mice showed lower activation of cDCs and impaired CXCR3‐dependant migration of NK cells to regional lymph nodes. This resulted in diminished formation of follicular helper CD4 + T cells leading to inferior induction of humoral response and lower production of high‐affinity virus‐specific antibodies in comparison to wild‐type mice. Abstract: NKp46/NCR1 is an activating NK‐cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1‐deficient (NCR1 gfp/gfp ) mice, we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK‐cell migration to regional lymph nodes. In addition, CD4 + T‐cell activation and follicular helper T‐cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B‐cell maturation. As a consequence, NCR1 gfp/gfp mice produced lower amounts of MCMV‐specific antibodies upon infection, which correlated with lower number of virus‐specific antibody secreting cells in analyzed lymph nodes.