期刊
MOLECULAR IMMUNOLOGY
卷 43, 期 11, 页码 1776-1790出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2005.11.003
关键词
B cell; autoimmunity; CD19; tolerance; anergy; transgenic mice
资金
- NCRR NIH HHS [5G12 RR03060-XX] Funding Source: Medline
- NIGMS NIH HHS [S06 GM08168] Funding Source: Medline
Mice transgenic for the R4A-C mu heavy chain of an anti-dsDNA antibody, maintain tolerance by anergy and deletion. In C57BL/6 mice overexpressing CD19, a molecule, which lowers the threshold for B cell activation, elevated levels of serum autoantibodies have been observed. In the present study, we wished to determine whether CD19 overexpression could alter the induction of tolerance in R4A-C mu mice and lead to the secretion of transgenic anti-dsDNA antibodies. We, therefore, bred R4A-C mu transgenic mice-to-mice transgenic for human CD19 (hCD19) and generated R4A-C mu mice heterozygous and homozygous for hCD19. We, now report the spontaneous secretion of transgenic IgM anti-dsDNA antibody in the sera of R4A-C mu mice overexpressing CD19, indicative of a loss of B cell tolerance. We observe that transgenic B cells secreting anti-dsDNA antibody in these mice are T independent and display a marginal zone like phenotype althought they do not reside in the MZ. In addition, they appear to be derived from the conventional B2 subset rather than the B I subset. Interestingly, a subset of the anti-dsDNA B cells in these mice still display the phenotype and functional characteristics of anergic B cells. These B cells cannot be activated to secrete antibody following BCR crosslinking, however, they are hyper-responsive to activation by innate signaling mechanisms. This Suggests that CD19 overexpression may promote anergic B cells to escape tolerance by converging with BCR independent pathways, thereby rendering these B cells hyper-responsive to innate signaling (c) 2005 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据