Gene analysis of antibodies specific for allergen and antigenrelating to autoimmunity

过敏原和自身免疫相关抗原特异性抗体的基因分析

• 批准号: 04454070
• 负责人: KAMINOGAWA Shuichi
• 金额: $ 4.03万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454070/
• 关键词: Immunoglobulin gene; Antibody Production; B cell; Peptide; beta-lacreglobulin; Food allevgy; MHC クラス II 分子; T細胞膜成分; IgE; クラススイッチ; ペプチド免疫; IgM産生B細胞クローン; B細胞ハイブリドーマ; gene usage; パラトープ構造

To elucidate the molecular and cellular mechanism of lgE-class switching leading to allergic diseases, we examined the differentiation process of antigen-specific B cells at a clonal level in related to the repertoire of helper T cells. We used a peptide fragment encompassing residues 25-40 (F25-40) of beta-lactoglobulin, which contained B cell determinant. T cell repertoire collaborating with F25-40-specific B cell were modified by priming with 1) beta-LG,2) F25-40-conjugated carrier protein or 3) F21-40. Thus, we demonstrate the helper functions of T cells in B cells differentiation at a clonal level by comparing primed B cell repertoire, class switching or affinity maturation among priming antigens. Consequently, the immunization with F21-40 could not induce strong lgG-class II switching. In addition, the restricted V_H gene usage (J558) was observed among B cell repertoire elicited by F21-40 distinct from other antigens. From these results, it has been suggested that T cell repertoire collaborating with B cells restrict B cell repertoire differentiating into Ab-secreting cells. To determine the molecular mechanism of the restriction, we analyzed the exact roles of the interaction between MHC class II molecules and T cell receptor on B cell activation. The results showed that the class II-mediated signals directly activate B cells and enhance lgG production. From these results, it has been suggested that the class II-mediated signals play an important role on the restriction of B cell repertoire and class switching.

为了阐明导致过敏性疾病的LGE级切换的分子和细胞机制，我们检查了与助手T细胞库相关的克隆水平上抗原特异性B细胞的分化过程。我们使用了包含25-40（F25-40）β-乳球蛋白的肽片段，其中含有B细胞决定因素。与F25-40特异性B细胞合作的T细胞库通过使用1）β-LG，2）F25-40偶联的载体蛋白或3）F21-40来修饰。因此，我们通过比较启动B细胞库，类切换或亲和力成熟的启动抗原的B细胞水平分化T细胞中T细胞在克隆水平上的辅助功能。因此，使用F21-40的免疫无法诱导强LGG级II转换。此外，在与其他抗原不同的F21-40引起的B细胞库中观察到了受限制的V_H基因使用率（J558）。从这些结果中，已经提出，与B细胞合作的T细胞库限制了B细胞库的分离为分泌AB的细胞。为了确定限制的分子机制，我们分析了MHC II类分子与T细胞受体在B细胞激活中相互作用的确切作用。结果表明，II类介导的信号直接激活B细胞并增强LGG产生。从这些结果中，已经提出，II类介导的信号在B细胞库和类切换的限制中起着重要作用。

项目成果

T.Hisatsune,A.Ametani,K.Nishijima,A.Enomoto S.Kaminogawa: "Strong Influence of the processing of the antigen on negative effects on T cell activation by regions outside the determinant area of bovine αSl-casein" Biosci.Biotech.Biochem. 56. 1616-1618 (1992

T.Hisatsune、A.Ametani、K.Nishijima、A.Enomoto S.Kaminokawa：“牛 αSl-酪蛋白决定区以外的区域对抗原加工对 T 细胞活化产生负面影响的强烈影响” Biosci .生物技术.生物化学。56。1616-1618（1992）

M.Hattori et al.: "Functional changes in β-loctoglobulin by conjugating with earboxymcthyl dextran" J.Agric.Food Chem.42. 2120-2125 (1994)

M.Hattori 等人：“与羧基甲基葡聚糖缀合对 β-球蛋白的功能变化”J.Agric.Food Chem.42 2120-2125 (1994)。

Y.Takahashi,他: "In vitro culture of primary B cells specific to a short peptide" Animall Cell Technology:Basic & Applied Aspects. 6. 299-303 (1994)

Y. Takahashi 等人：“短肽特异性原代 B 细胞的体外培养”动物细胞技术：基础与应用方面 (1994)。

T.Sakurai et al.: "Cryric B cell determinant in a short peptide:T cells do not induce antibody response to B cells when their determinants Overlap each other" Int,Immunol. 5. 793-800 (1993)

T.Sakurai 等人：“短肽中的 Cryric B 细胞决定簇：当 T 细胞的决定簇彼此重叠时，T 细胞不会诱导针对 B 细胞的抗体反应”Int，Immunol。

T.Sakurai et al.: "Cryptic B cell determinant in a short peptide : T cells do not induce antibody response to B cells when their determinants overlap each other" Int.Immunol.5. 793-800 (1993)

T.Sakurai 等人：“短肽中的隐性 B 细胞决定簇：当决定簇彼此重叠时，T 细胞不会诱导针对 B 细胞的抗体反应”Int.Immunol.5。