Requirement for cyclin D3 in germinal center formation and function

Jonathan U. Peled, J. Jessica Yu, Jeganathan Venkatesh, Enguang Bi, B. Belinda Ding, Melissa Krupski-Downs, Rita Shaknovich, Piotr Sicinski, Betty Diamond, Matthew D. Scharff, B. Hilda Ye

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes. Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes, little is known about how the GC-associated cell cycle is orchestrated. The D-type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes. Cell type- and developmental stage-specific roles of D-type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed. In this study, we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells. In contrast, GC development in Ccnd3 / mice is markedly impaired, as is the T cell-dependent antibody response. Within the GC, although both switched and unswitched B cells are affected by cyclin D3 inactivation, the IgM pool is more severely reduced. Interestingly, despite a compensatory increase in cyclin D2 expression, a significant number of Ccnd3 / GC B cells accumulate in quiescent G0 state. Lastly, although cyclin D3 inactivation did not disrupt BCL6 expression in GC B cells, it completely blocked the GC promoting effect of BCL6 overexpression, suggesting that cyclin D3 acts downstream of BCL6 to regulate GC formation. This is the first demonstration that cyclin D3 plays an important and unique role at the GC stage of B cell development.

Original languageEnglish (US)
Pages (from-to)631-646
Number of pages16
JournalCell Research
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2010

Keywords

  • B cell development
  • Cell cycle
  • Cyclin D3
  • Germinal center

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Peled, J. U., Yu, J. J., Venkatesh, J., Bi, E., Ding, B. B., Krupski-Downs, M., Shaknovich, R., Sicinski, P., Diamond, B., Scharff, M. D., & Ye, B. H. (2010). Requirement for cyclin D3 in germinal center formation and function. Cell Research, 20(6), 631-646. https://doi.org/10.1038/cr.2010.55