Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO

Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO
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DOI:
10.1084/jem.20012059
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发表时间:
2002-04-15
影响因子:
15.3
通讯作者:
Denzin, LK
Denzin, LK
中科院分区:
医学1区
文献类型:
--
作者:
Glazier, KS;Hake, SB;Denzin, LK

文献摘要

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通过MHC II类分子的肽获取由HLA-DM(DM)催化。在B细胞中,HLA-DO(DO)抑制或修饰DM的肽交换活性。我们发现DO蛋白水平在B细胞分化过程中受到调节。值得注意的是,相对于幼稚和记忆B细胞具有低水平DO的生发中心(GC)B细胞显示具有增强的抗原呈递能力。GC B细胞中DM蛋白水平也有所降低;然而,GC B细胞中DM与DO的比率显著增加,导致GC B细胞中更多的游离DM。我们的结论是DM和DO在B细胞分化的不同阶段的调制代表了B细胞调节其作为抗原呈递细胞的能力的机制。GC B细胞中的有效抗原呈递将促进GC B细胞-T细胞相互作用,这对于B细胞在GC中的正选择中存活是必需的。
Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation. Remarkably, germinal center (GC) B cells, which have low levels of DO relative to naive and memory B cells, are shown to have enhanced antigen presentation capabilities. DM protein levels also were somewhat reduced in GC B cells; however, the ratio of DM to DO in GC B cells was substantially increased, resulting in more free DM in GC B cells. We conclude that modulation of DM and DO in distinct stages of B cell differentiation represents a mechanism by which B cells regulate their capacity to function as antigen-presenting cells. Efficient antigen presentation in GC B cells would promote GC B cell-T cell interactions that are essential for B cells to survive positive selection in the GC.