Id2 negatively regulates B cell differentiation in the spleen
Id2 negatively regulates B cell differentiation in the spleen
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DOI：
10.4049/jimmunol.168.11.5507
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发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
Shachar, I
中科院分区：
文献类型：
--
作者：
Becker-Herman, S;Lantner, F;Shachar, I
B细胞发育的早期阶段发生在骨髓中，导致未成熟B细胞的形成。这些未成熟细胞迁移到脾脏，在那里它们分化成成熟（B2或边缘区（MZ））细胞。这一最后的成熟步骤对于B细胞变得对Ag有反应并参与免疫应答是至关重要的。Id 2是一种螺旋-环-螺旋蛋白，缺乏DNA结合区;因此，以显性负性方式抑制基本螺旋-环-螺旋功能。在这项研究中，我们发现，Id 2的表达下调的不成熟的B细胞分化成成熟的B2和MZ B细胞。在未成熟B细胞中表达的高水平的Id 2导致E2 A与E2盒位点的结合活性的抑制。此外，缺乏Id 2的小鼠显示脾中成熟B2细胞的比例升高，而这些小鼠中的MZ群体几乎不存在。因此，Id 2充当脾中发生的未成熟B细胞分化的调节剂，其负控制分化成成熟B2细胞，同时允许定型成MZ B细胞。在没有Id 2控制的情况下，未调节的分化指向成熟的B2群体。
Early stages of B cell development occur in the bone marrow, resulting in formation of immature B cells. These immature cells migrate to the spleen where they differentiate into mature (B2 or marginal zone (MZ)) cells. This final maturation step is crucial for B cells to become responsive to Ags and to participate in the immune response. Id2 is a helix-loop-helix protein that lacks a DNA-binding region; and therefore, inhibits basic helix-loop-helix functions in a dominant negative manner. In this study, we show that Id2 expression is down-regulated during differentiation of immature B cells into mature B2 and MZ B cells. The high levels of Id2 expressed in the immature B cells result in inhibition of E2A binding activity to an E2 box site. Moreover, mice lacking Id2 show an elevation in the proportion of mature B2 cells in the spleen, while the MZ population in these mice is almost absent. Thus, Id2 acts as a regulator of the differentiation of immature B cells occurring in the spleen, it negatively controls differentiation into mature B2 cells while allowing the commitment to MZ B cells. In the absence of Id2 control, the unregulated differentiation is directed toward the mature B2 population.