Defective B cell ontogeny and humoral immune response in mice prematurely expressing human complement receptor 2 (CR2, CD21) is similar to that seen in aging wild type mice

被引:4
作者
Twohig, Jason P. [2 ]
Pappworth, Isabel Y. [1 ]
Sivasankar, Baalasubramanian [2 ]
Kulik, Liudmila [3 ,4 ]
Bull, Melanie [2 ]
Holers, V. Michael [3 ,4 ]
Wang, Eddie C. Y. [2 ]
Marchbank, Kevin J. [1 ]
机构
[1] Univ Newcastle, Ctr Life, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England
[2] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales
[3] Univ Colorado, Dept Med, Denver, CO USA
[4] Univ Colorado, Dept Immunol, Denver, CO 80202 USA
基金
英国惠康基金; 英国医学研究理事会;
关键词
Transgenic/knockout; Complement; B lymphocytes; SIGNAL-TRANSDUCTION COMPLEX; GERMINAL CENTER DEVELOPMENT; T-DEPENDENT ANTIGENS; AGED MICE; ANTIBODY-RESPONSE; OLD MICE; MONOCLONAL-ANTIBODY; ACQUIRED-IMMUNITY; SENESCENT MICE; CR2(-/-) MICE;
D O I
10.1016/j.molimm.2009.03.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mice prematurely expressing human CR2 (hCR2) in the B cell lineage have a defective B cell ontogeny and humoral immune response. We have previously determined altered tyrosine phosphorylation patterns within hCR2 transgenic mice, suggesting that irreversible changes in B cell signaling pathways had occurred, which could explain the B cell unresponsiveness associated with hCR2 transgene expression. In support of that assertion, we found that increasing antigen dose or addition of adjuvant had a minimal impact on the ability of B cells to respond to antigen. However, analysis of aged hCR2 high mice (1 year plus) revealed that both B cell numbers, B cell sub-population distribution including expansion of a newly described B regulatory cell subset, and immune responses were comparable with age-matched hCR2 negative mice. Finally, we established that B cell unresponsiveness to antigen in aging wild type mice (1 year plus) was equivalent to that noted in 3-month-old hCR2(high) mice. This data provides evidence that 3-month-old hCR2high mice have a humoral immune system resembling aged mice and suggests that further examination of the precise molecular and cellular parallells between aged wild type mice and 3-month-old hCR2 high mice could provide an important insight into the mechanisms which lead to B cell unresponsiveness in the aging immune system. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2002 / 2013
页数:12
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