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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

Lookup NU author(s): Dr Isabel Pappworth, Professor Kevin MarchbankORCiD



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.

Publication metadata

Author(s): Twohig JP, Pappworth IY, Sivasankar B, Kulik L, Bull M, Holers VM, Wang EC, Marchbank KJ

Publication type: Article

Publication status: Published

Journal: Molecular Immunology

Year: 2009

Volume: 46

Issue: 10

Pages: 2002-2013

Date deposited: 10/06/2010

ISSN (print): 0161-5890

ISSN (electronic): 1872-9142

Publisher: Pergamon


DOI: 10.1016/j.molimm.2009.03.007

Notes: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't


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