B cell growth-promoting activity of recombinant human interleukin 4

• Published in: The Journal of immunology (1950) Vol. 139; no. 4; pp. 1135 - 1141
• Main Authors: Defrance, T, Vanbervliet, B, Aubry, JP, Takebe, Y, Arai, N, Miyajima, A, Yokota, T, Lee, F, Arai, K, de Vries, JE
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.08.1987; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; B-Lymphocytes - physiology; Biological and medical sciences; Cell Cycle - drug effects; Cell Division - drug effects; Drug Synergism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Growth Substances - pharmacology; Growth Substances - physiology; Humans; Immunobiology; Interferon-gamma - pharmacology; Interleukin-4; Lymphocyte Activation - drug effects; Lymphokines - pharmacology; Lymphokines - physiology; Lymphokines, interleukins ( function, expression); Recombinant Proteins; Regulatory factors and their cellular receptors; Time Factors; Human; Cell proliferation; Induction; Interleukin; Activation; Immune regulation; B-Lymphocyte; Lymphokine; Biological activity
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.139.4.1135

Human interleukin 4 (IL-4), also known as B cell stimulatory factor 1, is a T cell-derived glycoprotein consisting of 129 amino acids for which a cDNA has been recently isolated. IL-4 displays little or no B cell growth factor (BCGF) activity in the standard anti-IgM costimulatory assay using suboptimal concentrations of soluble anti-IgM antibody whereas the low m.w. BCGF is very active. When insolubilized anti-IgM was used as the costimulating agent, both IL-4 and the low m.w. BCGF were found to promote B cell proliferation. Human IL-4 is able to induce the proliferation of B lymphocytes preactivated for either 1 day with insolubilized anti-IgM antibody or for 3 days with Staphylococcus aureus strain Cowan I. However, IL-4 is poorly mitogenic for B cells preactivated for 1 day with the Staphylococcus strain whereas the low m.w. BCGF strongly enhances the proliferation of these B cells. These two findings demonstrate that the preactivation signal necessary to induce human B cells to proliferate in response to IL-4 is critical. The increased tritiated thymidine ([3H]dThd) uptake in preactivated B cell cultures with IL-4 reflects cel proliferation because cell cycle analysis demonstrates that IL-4 induces activated B cells to enter the S and G2/M phases of the cell cycle and the addition of IL-4 to preactivated B cell cultures permits the recovery of three- to fourfold more B cells after 4 days of culture. IL-4 and the low m.w. BCGF act in concert to induce the proliferation of anti-IgM-preactivated B cells as demonstrated by [3H]dThd uptake and cell cycle analysis. In striking contrast to the demonstrated antagonistic effect of interferon-gamma on the IL-4-induced expression of the low affinity receptor for IgE (Fc epsilon RL/CD23), on B cells, it was found that interferon-gamma enhanced the IL-4-induced proliferation of anti-IgM-preactivated B cells. Finally, it was found that IL-4 had to be present continuously during the culture period to exert an optimal growth-promoting effect on B cell blasts. As a conclusion, IL-4 is able to induce the proliferation of an appropriately activated subpopulation of human B cells.