التفاصيل البيبلوغرافية
| العنوان: |
Growth-factor receptor-bound protein-2 (Grb2) signaling in B cells controls lymphoid follicle organization and germinal center reaction. |
| المؤلفون: |
Ihn Kyung Jang, Cronshaw, Darran G., Luo-kun Xie, Guoqiang Fang, Jinping Zhang, Hyunju Oh, Yang-Xin Fu, Hua Gu, Yongrui Zou |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 5/10/2011, Vol. 108 Issue 19, p7926-7931, 6p |
| مصطلحات موضوعية: |
GROWTH factors, RADIOLIGAND assay, B cells, LABORATORY mice, TUMOR necrosis factors, CHEMOTAXIS, DENDRITIC cells |
| مستخلص: |
Grb2 (growth-factor receptor-bound protein-2) is a signaling adaptor that interacts with numerous receptors and intracellular signaling molecules. However, its role in B-cell development and function remains unknown. Here we show that ablation of Grb2 in B cells results in enhanced B-cell receptor signaling; however, mutant B cells do not form germinal centers in the spleen after antigen stimulation. Furthermore, mutant mice exhibit defects in splenic architecture resembling that observed in B-cell-specific lymphotoxin-β-deficient mice, including disruption of marginal zone and follicular dendritic cell networks. We find that grb2-/- B cells are defective in lymphotoxin-β expression. Although lymphotoxin can be up-regulated by chemokine CXCL13 and CD40 ligand stimulation in wild-type B cells, elevation of lymphotoxin expression in grb2-/- B cells is only induced by anti-CD40 but not by CXCL13. Our results thus define Grb2 as a nonredundant regulator that controls lymphoid follicle organization and germinal center reaction. Loss of Grb2 has no effect on B-cell chemotaxis to CXCL13, indicating that Grb2 executes this function by connecting the CXCR5 signaling pathway to lymphotoxin expression but not to chemotaxis. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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