INTERLEUKIN-4 AND SOLUBLE CD23 AS PROGRESSION FACTORS FOR HUMAN LYMPHOCYTES-B - ANALYSIS OF THEIR INTERACTIONS WITH AGONISTS OF THE PHOSPHOINOSITIDE DUAL PATHWAY OF SIGNALING

INTERLEUKIN-4 AND SOLUBLE CD23 AS PROGRESSION FACTORS FOR HUMAN LYMPHOCYTES-B - ANALYSIS OF THEIR INTERACTIONS WITH AGONISTS OF THE PHOSPHOINOSITIDE DUAL PATHWAY OF SIGNALING
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DOI:
10.1002/eji.1830181014
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发表时间:
1988-10-01
影响因子:
5.4
通讯作者:
GUY, GR
GUY, GR
中科院分区:
医学3区
文献类型:
--
作者:
GORDON, J;CAIRNS, JA;GUY, GR

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人B淋巴细胞预活化24小时与佛波醇二丁酸酯[P(Bu)2]和离子霉素的组合被发现提供了很好的目标,用于评估的详细行动的B细胞的进展因素。重组白细胞介素4(IL 4)和亲和纯化的25-kDa片段的CD 23分子(溶胶-CD 23)被证明是在这个试验中的活性。虽然IL 4的进展活性通过与P(Bu)2持续共培养而增强,但发现sol-CD 23的进展活性更严格地依赖于与佛波醇酯的这种联合应用。当使用刺激性CD 23抗体时,在预活化的B细胞中观察到触发细胞周期进展的类似要求。与P(Bu)2相反,离子霉素在这些测定中不增加IL 4或sol-CD 23,但显著增强抗CDw 40抗体的进展活性。当加入到B细胞同时,或之前,高剂量的佛波醇酯,IL 4出乎意料地下调随后的有丝分裂反应,这种代理,而当加入24小时后,IL 4上调这种刺激。后一种顺序的添加导致在B细胞表面上CD 23的特别显著的诱导,比当B细胞与单独的IL 4或与IL 4和P(Bu)2一起孵育时所看到的要多得多。这种表面CD 23的上调反过来又反映在这种培养物中出现大量可溶形式的分子。研究结果进行了讨论,通过参考可能的机制,IL 4和CD 23相互作用,发挥其多重作用的B细胞的调节途径。
Human B lymphocytes pre-activated for 24 h with a combination of phorbol dibutyrate [P(Bu)2] and ionomycin were found to provide excellent targets for assessing the detailed action of B cell progression factors. Both recombinant interleukin 4 (IL4) and affinity-purified 25-kDa fragment of the CD23 molecule (sol-CD23) were shown to be active in this assay. While the progression activity of IL4 was enhanced by continued co-culture with P(Bu)2, that of sol-CD23 was found to be more strictly dependent upon such a joint application with the phorbol ester. Similar requirements were observed for triggering cell-cycle progression in the pre-activated B cells when using a stimulating CD23 antibody. Ionomycin, in contrast to P(Bu)2, did not augment either IL4 or sol-CD23 in these assays but did enhance significantly the progression activity of an anti-CDw40 antibody. When added to B cells concomitantly with, or prior to, a high dose of phorbol ester, IL4 unexpectedly down-regulated the subsequent mitogenic response to this agent whereas, when added 24 h later, IL4 upregulated such stimulations. The latter sequence of additions resulted in a particularly dramatic induction of CD23 at the B cell surface, much more so than seen when B cells were incubated with either IL4 alone or with IL4 and P(Bu)2 together. This upregulation of surface CD23 was, in turn, mirrored by the appearance of large amounts of the soluble form of the molecule in such cultures. The findings are discussed with reference to possible mechanisms through which IL4 and CD23 interact to exert their multiple actions on B cell regulatory pathways.