| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Naoto Department of Biology, Institute for Medical Immunology, Kumamoto University Med, 医学部, 助手 (00166620)
HARADA Nobuyuki Department of Biology, Institute for Medical Immunology, Kumamoto University Med, 医学部, 助手 (40165022)
TOMINAGA Akira Department of Biology, Institute for Medical Immynology, Kumamoto University Med, 医学部, 助教授 (50172193)
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| Research Abstract |
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
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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
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