Depletion of Lyn kinase from the BCR complex and inhibition of B cell activation by excess CD21 ligation
Depletion of Lyn kinase from the BCR complex and inhibition of B cell activation by excess CD21 ligation
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DOI：
10.1093/intimm/14.2.139
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发表时间：
2002-02-01
影响因子：
4.4
通讯作者：
Weis, JH
中科院分区：
文献类型：
--
作者：
Chakravarty, L;Zabel, MD;Weis, JH
通过SCR和CD 21/CD 19/CD 81复合物的共连接，人和鼠CD 21基因产物已在功能上与B细胞活化相关。与抗原单独引起的刺激相比，与CD 21的补体配体复合的低水平抗原的结合增强了B细胞活化。缺乏功能性CD 21的小鼠容易发生自身免疫反应，这表明该受体也可能发挥负面作用：因此，在存在过量的携带补体的免疫复合物的情况下，B细胞抗原特异性激活可能会被抑制。使用细胞内钙激发分析来研究这种可能性，以跟踪BCR介导的激活。与单独的BCR连接相比，BCR和限量的CD 21受体的连接证明了预期的增强的细胞应答：单独的CD 21连接证明了钙通量没有改变。然而，BCR与过量CD 21结合的共连接导致钙应答的消除，表明CD 21连接下调BCR应答。与BCR和CD 21/CD 19/CD 81复合物相关的激酶的免疫沉淀证明，在与CD 21过量结合后，林恩优先从BCR复合物中耗尽。B细胞活化所必需的其他激酶的定位没有改变。这些数据表明，过量的CD 21配体结合可通过使林恩激酶与BCR复合物隔离而对B细胞活化产生负面影响。
The human and murine CD21 gene products have been functionally linked to B cell activation by the co-ligation of the SCR and the CD21/CD19/CD81 complexes. Binding of low levels of antigen complexed to the complement ligand(s) for CD21 enhances B cell activation compared to the stimulation caused by antigen alone. Mice lacking functional CD21 predispose to autoimmune responses suggesting that this receptor may also play a negative role: thus in the presence of excess complement-bearing immune complexes, B cell antigen-specific activation may be Inhibited. This possibility was investigated using intracellular calcium elicitation analyses to follow BCR-mediated activation. Ligation of the BCR and limiting quantities of the CD21 receptor demonstrated the expected enhanced cellular response compared to BCR ligation alone: CD21 ligation alone demonstrated no alteration in calcium flux. However, co-ligation of the BCR with excess CD21 binding resulted In the elimination of the calcium response, suggesting that CD21 ligation was down-modulating the BCR response. Immunoprecipitation of kinases associated with the BCR and CD21/CD19/CD81 complexes demonstrated that Lyn is preferentially depleted from the BCR complex following excess binding of CD21. Localization of other kinases integral for B cell activation is not altered. These data suggest that excess CD21 ligand binding can negatively impact B cell activation by sequestering Lyn kinase away from the BCR complex.