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Molecular analysis of clonal stability and longevity in B cell memory
C L Dell1, Y X Lu, J L Claflin
1Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor 48109.
Journal of Immunology (Baltimore, Md. : 1950)
|November 15, 1989
Summary
Dominant B cell clones, identified through adoptive transfer and genetic analysis, form the long-term memory cell population. Some memory B cells achieve stability by inactivating their mutation mechanisms.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- B cell memory is crucial for adaptive immunity.
- Understanding the clonal dynamics of B cell memory is essential for vaccine development and immunotherapy.
Purpose of the Study:
- To investigate the contribution of individual B cell clones to the establishment and maintenance of B cell memory.
- To determine the clonal relationships and genetic stability of memory B cells.
Main Methods:
- Adoptive transfer of spleen cells from immunized donor mice to irradiated recipients.
- Generation and sequencing of hybridomas to analyze immunoglobulin variable region genes (VH and VL).
- Study of DNA rearrangements at V region loci to ascertain clonal relationships.
Main Results:
- Adoptive transfer experiments demonstrated that progeny of dominant B cell clones constitute the memory cell population for extended periods.
- Identically mutated V genes were observed in hybridomas from paired recipients, indicating clonal expansion and selection.
- Evidence suggests that inactivation of the hypermutation mechanism contributes to the stability of some memory B cells.
Conclusions:
- A limited number of dominant B cell clones are responsible for generating long-lasting B cell memory.
- Memory B cell populations are shaped by clonal selection and expansion.
- Inactivation of somatic hypermutation is a mechanism for stabilizing memory B cells.