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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

Twohig, Jason Peter, Pappworth, Isabel Y., Baalasubramanian, Sivasankar, Kulik, Liudmila, Bull, Melanie, Holers, V. M., Wang, Edward Chung Yern and Marchbank, Kevin J. 2009. 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. Molecular Immunology 46 (10) , pp. 2002-2013. 10.1016/j.molimm.2009.03.007

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Abstract

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 hCR2(high) mice have a humoral immune system resembling aged mice and suggests that further examination of the precise molecular and cellular parallels 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Transgenic/knockout; Complement; B lymphocytes
Publisher: Elsevier
ISSN: 0161-5890
Last Modified: 06 Sep 2020 16:26
URI: http://orca-mwe.cf.ac.uk/id/eprint/25505

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