3 years ago

The Hajdu Cheney Mutation is a Determinant of B Cell Allocation of the Splenic Marginal Zone

The Notch2 receptor is a determinant of B cell function, and gain-of-NOTCH2–function mutations are associated with Hajdu Cheney Syndrome (HCS), a disease presenting with osteoporosis and acroosteolysis. We generated a mouse model reproducing the HCS mutation (Notch2HCS), and heterozygous global mutant mice displayed gain-of-Notch2 function. In the mutant spleen, the characteristic perifollicular rim marking the marginal zone (MZ), which is the interface between the non-lymphoid red pulp and the lymphoid white pulp, merged with components of the white pulp. As a consequence, the MZ of Notch2HCS mice occupied most of the splenic structure. To explore mechanisms involved, lymphocyte populations from the bone marrow and the spleen were harvested from heterozygous Notch2HCS mice and littermate sex-matched controls, and analyzed by flow cytometry. Notch2HCS mice had ∼5-fold increase in CD21/35highCD23- splenic MZ B cells and a proportional decrease in splenic follicular B cells (CD21/35intCD23+) at 1, 2, and 12 months of age. Western blot analysis revealed that the Notch2HCS mutant splenocytes had increased pAKT and pJNK, and gene expression analysis of spleen CD19+ B cells demonstrated induction of Hes1 and Hes5 in Notch2HCS mutants. Anti-Notch2 antibodies decreased MZ B cells in control and Notch2HCS mice. In conclusion, Notch2HCS mutant mice have an increase in mature B cells in the MZ of the spleen.

Publisher URL: www.sciencedirect.com/science

DOI: S0002944017306168

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.