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Mechanisms underlying generation and activation of class II MHC-restricted B lymphocytes and their function

II 类 MHC 限制性 B 淋巴细胞生成和激活的机制及其功能

基本信息

批准号：
02454189
负责人：
HAMAOKA Toshiyuki
金额：
$ 3.97万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454189/
关键词：
class II MHC B-lymphocyte MHC-restriction Surface Immunoglobulin B-lymphocyte Repertoire genetic control autoantibody signal Transduction クラスII MHC B細胞レパ-トリ-多クロ-ン性B細胞活性化自己免疫疾患 X染色体連鎖免疫不全 BーB細胞間相互作用 B細胞活性化 IーA分子 IーE分子 Ia

项目摘要

1. I-A molecules serve as restriction elements of the class 11 major histocompatibility complex (MHC) -restricted B-B cell interaction involved in the polyclonal B cell differentiation, but I-E molecules do not exhibit such activity. Moreover, cross-linking by anti-I-E mAb of I-E molecules on B cells induces increases in intracellular CAMP levels, whereas such increases are not elicited by cross-linking of I-A molecules, indicating disparate function of I-A and I-E molecules expressed on B cells.2. The B lymphoma cells expressing relevant I-A molecules function as auxiliary cells in the class II MHC-restricted B cell activation, While neither I-A-positive macrophage lines nor I-A-transfected fibroblasts collaborate with class II NMC-restricted B cells. Thus, B-cell unique signals play a critical role in the B-cell activation.3. It is shown that there exist at least two distinct mechanisms in the T-independent B cell activation pathway. Anti-trinitrophenyl (TNP) antibody responses induced by LPS require class 11 MHC-restricted B-B cell inter-action but not surface Ig-mediated signaling, whereas those evoked by TNP-LPS con ugates are dependent on signaling through surface Ig but not by class 11 MHC molecules. This implies that signal transduction through surface Ig overcomes the requirement for class 11 MHC-mediated signaling.4. In the anti-BrMRBC (bromelain-treated mouse red blood cell) autoantibody responses induced by LPS, genotypically low-responder B cells are converted to highresponder phenotype if the low-responder B cells mature under the conditions in which they are able to acquire the restriction specificity for high-responder type of class 11 MHC molecules.

1. I-A分子是11类主要组织相容性复合体（MHC）限制的B-B细胞相互作用的限制性元件，参与多克隆B细胞分化，但I-E分子不表现出这种活性。此外，B细胞上I-E分子的抗I-E单抗交联诱导细胞内CAMP水平升高，而I-A分子的交联不会引起这种升高，这表明B细胞上表达的I-A和I-E分子的功能不同。表达相关I-A分子的B淋巴瘤细胞在II类mhc限制性B细胞活化中起辅助细胞的作用，而I-A阳性巨噬细胞系和I-A转染的成纤维细胞都不能与II类nmc限制性B细胞协同作用。因此，b细胞的独特信号在b细胞活化中起着至关重要的作用。结果表明，在t非依赖性B细胞激活途径中至少存在两种不同的机制。LPS诱导的抗三硝基苯（TNP）抗体反应需要11类MHC限制性B-B细胞相互作用，而不需要表面Ig介导的信号传导，而TNP-LPS偶联物诱发的抗体反应依赖于通过表面Ig而不是11类MHC分子的信号传导。这意味着通过表面Ig进行信号转导克服了11类mhc介导信号的要求。在LPS诱导的抗brmrbc（菠萝蛋白酶处理的小鼠红细胞）自身抗体反应中，如果低应答B细胞在能够获得高应答型11类MHC分子的限制性特异性的条件下成熟，则基因典型的低应答B细胞会转化为高应答表型。