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.
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.
Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK.
Jason P
JP
Twohig
Isabel Y
IY
Pappworth
Baalasubramanian
B
Sivasankar
Liudmila
L
Kulik
Melanie
M
Bull
V Michael
VM
Holers
Eddie C Y
EC
Wang
Kevin J
KJ
Marchbank
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000375:Aging / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007136:Immunoglobulins / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D017464:Receptors, Complement 3d / Q000276:immunology*; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000941:Antigens; D007136:Immunoglobulins; D017464:Receptors, Complement 3d