期刊
MOLECULAR IMMUNOLOGY
卷 45, 期 7, 页码 1883-1892出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2007.10.041
关键词
activation-induced DNA cytosine deaminase; somatic hypermutation; class switch recombination; immunoglobulin; transgenic mice
资金
- NIAID NIH HHS [AI052400, R01 AI052400-05A2, R56 AI047380, R01 AI053130, R01 AI047380, R01 AI052400, AI053130, R01 AI047380-07, R01 AI053130-05] Funding Source: Medline
Activation-induced DNA cytidine deaminase (AID) is required for somatic hypermutation (SHM) and efficient class switch recombination (CSR) of immunoglobulin (Ig) genes. We created AID-transgenic mice that express AID ubiquitously under the control of a P-actin promoter. When crossed with AID-/- mice, the AID-transgenic, AID-/- mice carried out SHM and CSR, showing that the AID transgenes were functional. However, the frequencies of SHM in V- and switch-regions, and CSR were reduced compared to those in a wild type AID background. Several criteria suggested that the inefficiency of SHM was due to reduced AID activity, rather than lack of recruiting error-prone DNA repair. High levels of AID mRNA were produced in resting B cells and kidney, cells that do not express AID in wild type mice. Compared with these cells, activated B cells expressed about an order of magnitude less AID mRNA suggesting that there may be a post-transcriptional mechanism that regulates AID mRNA levels in professional AID producers but not other cells. The AID protein expressed in resting B cells and kidney was phosphorylated at serine-38. Despite this modification, known to enhance AID activity, resting B cells did not undergo SHM. Apparently, the large amounts of AID in resting B cells are not targeted to Ig genes in vivo, in contrast to findings in vitro. (C) 2007 Elsevier Ltd. All rights reserved.
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