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Requirement for cyclin D3 in germinal center formation and function
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Journal Article
Requirement for cyclin D3 in germinal center formation and function
2010
Overview
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 cyclln D2 expression, a significant number of Ccnd3^-/- GC B cells accumulate in quiescent GO 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Cell Differentiation - genetics
/ Cell Differentiation - immunology
/ Germinal Center - immunology
/ Germinal Center - metabolism
/ Humans
/ Lymphocyte Activation - genetics
/ Lymphocyte Activation - immunology
/ Lymphoid Tissue - immunology
/ Lymphoid Tissue - metabolism
/ Mice
/ 体液免疫反应
/ 免疫球蛋白M
/ 发育阶段特异性
/ 气相色谱
/ 细胞周期素
/ 细胞周期蛋白
/ 维生素D3
