Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5918106 | Molecular Immunology | 2013 | 12 Pages |
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 hCR2high 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 hCR2high 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 hCR2high mice could provide an important insight into the mechanisms which lead to B cell unresponsiveness in the aging immune system.
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Authors
Jason P. Twohig, Isabel Y. Pappworth, Baalasubramanian Sivasankar, Liudmila Kulik, Melanie Bull, V. Michael Holers, Eddie C.Y. Wang, Kevin J. Marchbank,