S Cayphas

B cell growth modulating and differentiating activity of recombinant human 26-kd protein (BSF-2, HuIFN-beta 2, HPGF)

The human ‘26‐kd protein’ is a secreted glycoprotein expressed, for example, in (blood) leukocytes, in epithelial cells treated with various inducers, but most strongly in interleukin‐1 (IL‐1)‐treated fibroblasts. After finding it has antiviral and 2‐5A synthetase‐inducing activity, one group of authors called this protein IFN‐beta 2. However, recently the full‐length 26‐kd cDNA sequence was shown to be identical with that of a B‐cell‐differentiating lymphokine called BSF‐2, and another report suggested that the 26‐kd protein could support the growth of some transformed murine B cell lines. To define its biological activities, we expressed the recombinant 26‐kd protein by translating in Xenopus laevis oocytes a pure, synthetic chimeric mRNA containing the 26‐kd protein coding region surrounded by Xenopus laevis beta‐globin untranslated regions. A similar construction, but containing the HuIFN‐beta cDNA coding region, was used to produce HuIFN‐beta by the same procedure. Both recombinant glycoproteins were secreted, glycosylated, and their amounts were measured by [35S]methionine incorporation by the oocyte. Here we show that the recombinant 26‐kd protein exhibits a high growth factor activity when assayed on an IL‐HP1‐dependent murine B cell hybridoma (sp. act. approximately 2 X 10(8) U/mg) as well as a potent differentiating activity on human CESS cells (sp. act. approximately 5 X 10(7) U/mg). While rHuIFN‐beta was inactive in the latter two assays, it had the expected antiviral activity of 1‐5 X 10(8) U/mg. The parallel recombinant 26‐kd protein preparations had no detectable antiviral activity (i.e. a maximal specific activity of 1‐3 X 10(2) U/mg, if any). The 26‐kd protein is thus clearly an interleukin, and considering the confusing nomenclature now in use, this factor may better be renamed ‘interleukin 6’.

The Interrelationship Between Interleukin-1, Interferon-β and Hemopoietic Growth Factors

Cytokines are humoral factors which play an important role in immunity. They are produced in extremely small quantities, but can be detected in vitro due to their very high specific activity in various biological tests, such as growth assays, in which they are active at the ng level. By the use of advanced purification methods and recombinant techniques, research on identification and production of a number of cytokines has made a tremendous progress. Thus, it has become clear that several biologically defined factors correspond to the same molecular structure.