Regulation of B cell growth and differentiation and immune abnormality

点击翻译按钮获取中文摘要

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