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Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
Requirement for cyclin D3 in germinal center formation and function
Jonathan U Peled1, J Jessica Yu, Jeganathan Venkatesh
1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cell Research
|April 21, 2010
Summary
Cyclin D3 is crucial for germinal center (GC) development and antibody responses, despite not being essential for B cell proliferation in vitro. Its absence impairs GC formation and B cell selection.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Germinal centers (GCs) are vital for high-affinity antibody production.
- B cells in GCs undergo rapid proliferation, selection, and antibody gene diversification.
- The cell cycle regulation within GCs is not fully understood, particularly the role of D-type cyclins.
Purpose of the Study:
- To investigate the role of cyclin D3 in the GC reaction and humoral immune response.
- To determine if cyclin D3 is required for B cell proliferation and Ig class switching in vitro.
- To elucidate the function of cyclin D3 in GC development and B cell selection in vivo.
Main Methods:
- Analysis of B cell proliferation and Ig class switching in vitro.
- Phenotypic analysis of GC B cells in cyclin D3-deficient (Ccnd3(-/-)) mice.
- Assessment of T cell-dependent antibody responses in Ccnd3(-/-) mice.
- Investigation of BCL6 expression and function in the context of cyclin D3 deficiency.
Main Results:
- Cyclin D3 is dispensable for in vitro B cell proliferation and Ig class switching.
- GC development and T cell-dependent antibody responses are severely impaired in Ccnd3(-/-) mice.
- Ccnd3(-/-) GC B cells show reduced IgM(-) pools and accumulation in the G0 phase, despite increased cyclin D2.
- Cyclin D3 acts downstream of BCL6, as it is required for BCL6's GC-promoting effects.
Conclusions:
- Cyclin D3 plays a critical and unique role in GC formation and B cell selection during the humoral immune response.
- The absence of cyclin D3 leads to impaired GC development and antibody production.
- Cyclin D3 is essential for the proper cell cycle progression of GC B cells, acting downstream of BCL6.
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