CD1d and CD1c Expression in Human B Cells Is Regulated by Activation and Retinoic Acid Receptor Signaling
CD1d and CD1c Expression in Human B Cells Is Regulated by Activation and Retinoic Acid Receptor Signaling
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DOI：
10.4049/jimmunol.1003615
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
van den Elzen, Peter
中科院分区：
文献类型：
--
作者：
Allan, Lenka L.;Stax, Annelein M.;van den Elzen, Peter
B细胞对蛋白Ags的激活和Ab的产生需要提供肽来募集T细胞的帮助。我们和其他人最近已经证明B细胞也可以通过CD1d向NKT细胞呈递脂质Ags来获得先天帮助。鉴于NKT细胞对体液免疫的新发现，我们试图确定调节人类B细胞中CD1分子表达的途径。我们发现离体、激活和记忆B细胞与静止、初始和边缘区样B细胞相比表达较低水平的CD1d。在体外，CD1d被所有形式的B细胞激活下调，留下一个狭窄的时间窗口，B细胞可以激活NKT细胞。CD1c的表达和功能也在CD40L单独激活后下降，而通过BCR激活可显著上调CD1c，特别是在边缘区样B细胞上。我们发现，cd40l诱导的CD1d和CD1c的下调与维甲酸受体a （RAR α）反应基因的表达减少相关，这种效应被RAR α激动剂逆转。然而，bcr诱导的CD1c上调不依赖于RAR途径。我们的研究发现，在人B细胞中，CD1d和CD1c都被RAR α信号上调，这与在树突状细胞中报道的CD1c被反向下调的效应不同。维甲酸上调CD1d的一个功能后果是NKT细胞对B细胞的细胞毒性。这些结果对我们理解cd1限制性T细胞如何控制体液免疫至关重要。免疫学杂志，2011,18(6):5261-5272。
B cell activation and Ab production in response to protein Ags requires presentation of peptides for recruitment of T cell help. We and others have recently demonstrated that B cells can also acquire innate help by presenting lipid Ags via CD1d to NKT cells. Given the newfound contribution of NKT cells to humoral immunity, we sought to identify the pathways that regulate CD1 molecule expression in human B cells. We show that ex vivo, activated and memory B cells expressed lower levels of CD1d compared with resting, naive, and marginal zone-like B cells. In vitro, CD1d was downregulated by all forms of B cell activation, leaving a narrow temporal window in which B cells could activate NKT cells. CD1c expression and function also decreased following activation by CD40L alone, whereas activation via the BCR significantly upregulated CD1c, particularly on marginal zone-like B cells. We found that the CD40L-induced downreglation of CD1d and CD1c correlated with diminished expression of retinoic acid receptor a (RAR alpha) response genes, an effect that was reversed by RAR alpha agonists. However, BCR-induced upregulation of CD1c was independent of the RAR pathway. Our findings that both CD1d and CD1c are upregulated by RAR alpha signaling in human B cells is distinct from effects reported in dendritic cells, in which CD1c is inversely downregulated. One functional consequence of CD1d upregulation by retinoic acid was NKT cell cytotoxicity toward B cells. These results are central to our understanding of how CD1-restricted T cells may control humoral immunity. The Journal of Immunology, 2011, 186: 5261-5272.