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
| Autor: | Baalasubramanian Sivasankar, Kevin J. Marchbank, Edward Chung Yern Wang, Isabel Y. Pappworth, VM Holers, Melanie J. Bull, Liudmila Kulik, Jason Peter Twohig |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Aging
Erythrocytes Time Factors Complement receptor 2 Transgene Immunology Complement Immunoglobulins Mice Transgenic Article 03 medical and health sciences Mice 0302 clinical medicine Immune system Antigen Adjuvants Immunologic medicine Animals Humans Antigens Molecular Biology B cell 030304 developmental biology 0303 health sciences B-Lymphocytes Sheep biology Transgenic/knockout Germinal center Germinal Center Lymphocyte Subsets B-1 cell medicine.anatomical_structure Phenotype Immune System Antibody Formation biology.protein Receptors Complement 3d Antibody Spleen 030215 immunology B lymphocytes |
| Zdroj: | Molecular Immunology |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2009.03.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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