B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes.
B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes.
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DOI：
10.1073/pnas.92.8.3348
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发表时间：
1995-04
影响因子：
11.1
通讯作者：
H. Wortis;M. Teutsch;M. Higer;J. Zheng;D. Parker
中科院分区：
文献类型：
--
作者：
H. Wortis;M. Teutsch;M. Higer;J. Zheng;D. Parker
用抗 IgM（一种 T 依赖性 2 型抗原的类似物）的可溶性 F(ab')2 片段处理静止的小 B 细胞，诱导其活化，其特征是增殖和表面 CD5 的表达。相比之下，B细胞响应由固定的活化T辅助2细胞或可溶性CD40配体-CD8 (CD40L)重组蛋白提供的胸腺依赖性诱导信号而诱导增殖，表现出CD23（Fc epsilon II受体）水平升高，并且没有表面CD5。使用抗 IgM 和 CD40L 治疗可诱导更高水平的增殖，并产生单一 B 细胞群，共表达极少量的 CD5，而 CD23 仅有轻微升高。抗 IgM 介导的激活对环孢菌素 A 和 FK520 的抑制高度敏感，但 CD40L 介导的激活则不然。 Sp-cAMPS 是 cAMP 的类似物，可增强 CD40L 并抑制表面 IgM 介导的激活。综合起来，这些结果被解释为意味着存在单一的小型静息 B 细胞群，可以对 T 不依赖的 2 型（表面 IgM）或 T 依赖的 (CD40) 介导的激活作出反应。为了响应不同的细胞内信号，这些细胞被诱导进入替代的分化途径。
Treatment of small resting B cells with soluble F(ab')2 fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activation characterized by proliferation and the expression of surface CD5. In contrast, B cells induced to proliferate in response to thymus-dependent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein displayed elevated levels of CD23 (Fc epsilon II receptor) and no surface CD5. Treatment with anti-IgM and CD40L induced higher levels of proliferation and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclosporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these results are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surface IgM)- or T-dependent (CD40)-mediated activation. In response to different intracellular signals these cells are induced to enter alternative differentiation pathways.