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Evolution of B-cell clonal expansions with age
Paul Szabo1, Fang Li, Joel Mathew
1Division of Geriatrics and Gerontology, Weill Medical College of Cornell University, NY 10021, USA.
Cellular Immunology
|May 28, 2005
Summary
B-cell clonal expansions (BCE) are transient in young mice but persist in older mice. This study suggests persistent BCE in aged mice may evolve from early-life transient expansions, potentially leading to B-cell lymphomas.
Area of Science:
- Immunology
- Aging Research
- Cancer Biology
Background:
- B-cell clonal expansions (BCE) are short-lived in young mice but persist longer in aged mice.
- The extended survival of BCE in older mice is not solely due to host age.
- This suggests a developmental process for persistent BCE over time.
Purpose of the Study:
- To investigate the hypothesis that persistent BCE in aged mice develop from transient BCE earlier in life.
- To determine if benign, persistent BCE can evolve into B-cell lymphomas.
Main Methods:
- Young C57BL/6 mice were immunized with hen egg lysozyme (HEL).
- Mice were monitored for the development of persistent BCE and serum mIg.
- Benign BCE in 18-month-old mice were analyzed for evolution into lymphomas by 29 months of age.
- IgH mRNA CDR3 sequencing was used to trace lymphoma origins.
Main Results:
- The majority of mice developed benign, persistent BCE associated with HEL-specific serum mIg by 28 months.
- Four of eight mice developed diffuse large cell lymphomas by 29 months.
- In one case, lymphoma IgH mRNA CDR3 sequence was derived from a persistent BCE identified 11 months prior.
Conclusions:
- Observations support the hypothesis that persistent BCE and B-cell lymphomas arise from stepwise genetic alterations and Darwinian selection.
- This process transforms transient early-life BCE into long-term expansions and malignancies in older mice.