Regulation of B cell growth and differentiation and immune abnormality

B细胞生长分化及免疫异常的调节

• 批准号: 61480159
• 负责人: TAKATSU Kiyoshi
• 金额: $ 4.1万
• 依托单位: Kumamoto University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480159/
• 关键词: B Cell Growth And Differentiation; T Cell Replacing Factor (TRF.); B細胞増殖分化; TRF; B151K12; B細胞増殖分化因子; BCGF【II】; 抗TRF抗体; 単クローン抗体; TRF cDNA; pSP6K-mTRF23

TRF has originally been defined as a T-cell-derived lymphokine that triggers activated B cells for a terminal differentiation into Ig-secretring cell. HPLC-purified TRF from Sup of a murine TRF-produ- cing B151 cells is a acidic glycoprotein, exerts BCGF II activity and induces expression of IL-2 receptors. It does not show IL-1, IL-2, IL-3, BSF-1/IL-4, or IFN<gamma> activity. We prepared monoclonal TB13 and NC17 antibodies against HPLC-purified B151-TRF which is specific for and can inhibit TRF as well as BCGF II activity of B151-TRF. Moreover, TB13 as well as NC17 antibody can immynoprecipitate 46 Kd molecule from B151 Sup which wxerts TRF as well as BCGF II Activity.Complementary DNA (pSP6K-mTRF23) encoding for murine TRF/IL-5 was cloned and its entire nucleotide sequences were determined. The nurine TRF/IL-5 cDNA encodes 133 amino acids including N-terminal strongly hydrophobic regions. Secreted recombinant TRF-IL-5 (apparent m.w. of 46 Kd) has 113 amino acid residues and also comp … More rise of homodimers of a molecule with an apparent m.w. of 25 to 30 Kd. TRF/IL-5 mRNA is constitutively expressed in constitutively TRF-producing B151 and is inducible in some T cell lines upon stimulation with PMA or Con A. TRF/IL-5 mRNA is also expressed in Tbc-primed T cells upon the stimulation with PPD, whereas its expression is not effectively induced in non-primed spleen cells by the stimlation with Con A or PMA plus calcium ionophore.The translation product of murine TRF/IL-5 cDNA triggers resting as well as activated (DNP-primed or LPS-stimylated) murine B cells for terminal differentiation into Ig-secreting cells (IgM, IgGl, or IgA) in accompanying with increased mRNA expression for secreted forms of relevant Ig heavy chain (m, <gamma>, ro<alpha>). Among them, increases in the level of<mu>- and <alpha>-specific mRNA for the secreted form of IgM and IgA, respectively, were prominent. Moreover, TRF/IL-5 induce maturation of resting B cells into IgM-secreting cells. TRF/IL-5 promotes growth of activated B cells as well as BCL_1 cells. TRF-IL-5 is, therefore, a growth as well as a differentiation inducing factor for B cells. Moreover, it induces functional IL-2 receptors on_+ resting as well as activated B cells besides TRF and BCGF II activities. TRF/IL-5 acts also on PNA^+ thymocytes as killer-helper factor which can induce not only expression of IL-2 receptors on PNA^+ thymocytes, but also generation of CTL in conjunction of IL-2. Colony formation of eosinophil in bone marrow culture was also supported by TRF/IL-5, and terminanal differentiation of eosinophilopoitic cells are preferntially stimylated by TRF/IL-5.TRF-IL-5 triggers its targets through specific receptors which appears to have an apparent molecular mass of 47 Kd. There seems to be two sets of TRF-IL-5, high- and low-affinity, receptors. Less

TRF最初被定义为T细胞衍生的淋巴因子，其触发活化的B细胞终末分化为Ig分泌细胞。从小鼠TRF产生细胞中提取的TRF是一种酸性糖蛋白，具有BCGF Ⅱ活性，并诱导IL-2受体的表达。它不显示IL-1、IL-2、IL-3、BSF-1/IL-4或IFN<gamma>活性。我们制备了针对HPLC纯化的B151-TRF的单克隆抗体TB 13和NC 17，其特异性地针对并且可以抑制TRF以及B151-TRF的BCGF II活性。TB_（13）和NC_（17）抗体均能免疫沉淀B_151细胞上的46 KD分子，该分子具有TRF和BCGF Ⅱ的活性。Nurine TRF/IL-5 cDNA编码133个氨基酸，包括N端强疏水区。分泌的重组TRF-IL-5（表观m.w.的46 Kd）具有113个氨基酸残基，并且还具有与其它氨基酸残基相同的氨基酸残基。 ...更多信息 具有表观分子量的分子的同源二聚体的增加25到30 kD。TRF/IL-5 mRNA在组成型产生TRF的B151中组成型表达，并且在PMA或Con A刺激后在某些T细胞系中可诱导。Tbc致敏的T细胞经PPD刺激后也表达TRF/IL-5 mRNA，而未致敏的脾细胞经ConA或PMA加钙离子载体刺激后TRF/IL-5 mRNA的表达均未被有效诱导。（DNP-致敏或LPS-刺激的）鼠B细胞用于终末分化为Ig-分泌细胞（IgM、IgG 1或伊加），伴随相关IG重链（m、ro）的分泌形式的mRNA表达增加<gamma><alpha>。其中，<mu><alpha>IgM和伊加的分泌形式的特异性mRNA水平的增加，分别是突出的。此外，TRF/IL-5诱导静息B细胞成熟为IgM分泌细胞。TRF/IL-5促进活化的B细胞和BCL_1细胞的生长。因此，TRF-IL-5是B细胞的生长和分化诱导因子。此外，除了TRF和BCGF II活性外，它还诱导_+静息和活化B细胞上的功能性IL-2受体。TRF/IL-5还可作为一种免疫辅助因子作用于PNA^+胸腺细胞，不仅可诱导PNA^+胸腺细胞表达IL-2受体，还可与IL-2结合产生CTL。TRF/IL-5也支持骨髓培养中嗜酸性粒细胞的集落形成，并且TRF/IL-5优选刺激嗜酸性粒细胞的终末分化。TRF-IL-5通过表观分子量为47 Kd的特异性受体触发其靶点。似乎存在两组TRF-IL-5，高亲和力和低亲和力受体。少

项目成果

Haraka,N.: "Production of a monoclonal antibody useful in the molecular characterizaton of murine T-cell replacing factor/B cell growth factor II." Proceedings of the National Academy of Sciences of the U.S.A.84. 4581-4585 (1987)

Haraka,N.：“生产可用于小鼠 T 细胞替代因子/B 细胞生长因子 II 分子表征的单克隆抗体。”

Tominaga, A.: Journal of Immunology. 140. 1175-1182 (1988)

富永，A.：免疫学杂志。

Matsumoto,M.: "Role of T cell-replacing factor (TRF) in the murine B cell differentiation: induction of increased levels of expression of secreted type IgM mRNA." Journal of Immunology. 138. 1826-1833 (1987)

Matsumoto,M.：“T 细胞替代因子 (TRF) 在小鼠 B 细胞分化中的作用：诱导分泌型 IgM mRNA 表达水平增加。”

Kinashi,T.: Nature. 324. 70-73 (1986)

Kinashi,T.：自然。

Kikuchi,Y.: Journal of Immunology. 136. 3553-3560 (1986)

菊池，Y.：免疫学杂志。