Human CD22 Inhibits Murine B Cell Receptor Activation in a Human CD22 Transgenic Mouse Model
| العنوان: | Human CD22 Inhibits Murine B Cell Receptor Activation in a Human CD22 Transgenic Mouse Model |
|---|---|
| المؤلفون: | Tadimeti S. Rao, Britni M. Arlian, Romain Ballet, Eugene C. Butcher, Elena Shanina, Michael D. Kulis, Shiteng Duan, Edward P. Connors, James C. Paulson, Joana Juan, Kyle J. Bednar, Wai-Ping Fung-Leung, Matthew S. Macauley |
| المصدر: | The Journal of Immunology. 199:3116-3128 |
| بيانات النشر: | The American Association of Immunologists, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Genetically modified mouse, Transgene, Immunology, CD22, Naive B cell, B-cell receptor, SIGLEC, Biology, Molecular biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Antigen, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, medicine, Immunology and Allergy, B cell |
| الوصف: | CD22, a sialic acid–binding Ig-type lectin (Siglec) family member, is an inhibitory coreceptor of the BCR with established roles in health and disease. The restricted expression pattern of CD22 on B cells and most B cell lymphomas has made CD22 a therapeutic target for B cell–mediated diseases. Models to better understand how in vivo targeting of CD22 translates to human disease are needed. In this article, we report the development of a transgenic mouse expressing human CD22 (hCD22) in B cells and assess its ability to functionally substitute for murine CD22 (mCD22) for regulation of BCR signaling, Ab responses, homing, and tolerance. Expression of hCD22 on transgenic murine B cells is comparable to expression on human primary B cells, and it colocalizes with mCD22 on the cell surface. Murine B cells expressing only hCD22 have identical calcium (Ca2+) flux responses to anti-IgM as mCD22-expressing wild-type B cells. Furthermore, hCD22 transgenic mice on an mCD22−/− background have restored levels of marginal zone B cells and Ab responses compared with deficiencies observed in CD22−/− mice. Consistent with these observations, hCD22 transgenic mice develop normal humoral responses in a peanut allergy oral sensitization model. Homing of B cells to Peyer’s patches was partially rescued by expression of hCD22 compared with CD22−/− B cells, although not to wild-type levels. Notably, Siglec-engaging antigenic liposomes formulated with an hCD22 ligand were shown to prevent B cell activation, increase cell death, and induce tolerance in vivo. This hCD22 transgenic mouse will be a valuable model for investigating the function of hCD22 and preclinical studies targeting hCD22. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::166b57f00f820888de1ae19bdf046a8dTest https://doi.org/10.4049/jimmunol.1700898Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........166b57f00f820888de1ae19bdf046a8d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
|---|