Human B cell growth factor enhances proliferation and glial fibrillary acidic protein gene expression in rat astrocytes

Abstract

The proliferation and differentiation of astrocytes are fundamental events in the normal development and function of the central nervous system (CNS), and may also contribute to the pathogenesis of a number of neurological diseases. Products of T lymphocytes can stimulate proliferation of astrocytes, but the nature of the T lymphocyte-derived molecule(s) responsible for this response is unknown. The present study was undertaken to examine several well-characterized T lymphocyte-derived factors for their ability to stimulate cultured primary rat astrocytes. While recombinant human interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and rat or human recombinant interferon-gamma (IFN-gamma) have no proliferative effect on astrocytes, a human T cell-derived B cell growth factor (BCGF) does. This BCGF, termed 2B11, had previously been characterized by its ability to enhance the proliferation of anti-mu-stimulated human B cells, while not influencing B cell immunoglobulin synthesis. High performance liquid chromatography (HPLC)-purified 2B11-BCGF (MW approximately 20,000 daltons) stimulates the proliferation of astrocytes in a dose-dependent fashion. Purified 2B11-BCGF also induced morphological differentiation and increased mRNA transcripts for glial fibrillary acidic protein (GFAP) in rat astrocytes. In addition to demonstrating the absence of effect of other known lymphokines, the effect on astrocytes attributed to 2B11-BCGF was confirmed by blocking its activity with a monoclonal antibody specific for 2B11-BCGF. Absorption experiments demonstrated that when BCGF activity was absorbed out by large, activated human B cells, astrocyte-stimulatory activity was also depleted. Rat astrocytes were able to partially absorb out both BCGF and astrocyte-stimulatory activity. These results suggest that 2B11-BCGF is responsible for stimulating astrocyte proliferation, and that human B cells and rat astrocytes may share a similar receptor for BCGF. These findings indicate that the growth and differentiation of astrocytes can be influenced by a T cell-derived lymphokine, 2B11-BCGF, whose activity thus far appears to be distinct from other reported cytokines.