Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes

• Published in: The Journal of immunology (1950) Vol. 137; no. 12; pp. 3855 - 3860
• Main Authors: Kehrl, JH, Roberts, AB, Wakefield, LM, Jakowlew, S, Sporn, MB, Fauci, AS
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.12.1986; American Association of Immunologists
• Subjects: Adolescent; Adult; Analysis of the immune response. Humoral and cellular immunity; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - secretion; Biological and medical sciences; Cell Differentiation - drug effects; Cell Division - drug effects; Child; Depression, Chemical; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunoglobulins - secretion; Interleukin-2 - antagonists & inhibitors; Miscellaneous; Peptides - pharmacology; Peptides - secretion; Receptors, Cell Surface - metabolism; Receptors, Transforming Growth Factor beta; Regulatory factors and their cellular receptors; Transforming Growth Factors; Autoregulation; Human; Cell proliferation; Proteins; Membrane receptor; Transforming growth factor β; Biosynthesis; Immune regulation; B-Lymphocyte; Cell differentiation; Biological activity
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.137.12.3855

The growth and differentiation of B cells to immunoglobulin (Ig)-secreting cells is regulated by a variety of soluble factors. This study presents data that support a role for transforming growth factor (TGF)-beta in this regulatory process. B lymphocytes were shown to have high-affinity receptors for TGF-beta that were increased fivefold to sixfold after in vitro activation. The addition of picogram quantities of TGF-beta to B cell cultures suppressed factor-dependent, interleukin 2 (IL 2) B cell proliferation and markedly suppressed factor-dependent (IL 2 or B cell differentiation factor) B cell Ig secretion. In contrast, the constitutive IgG production by an Epstein Barr virus-transformed B cell line was not modified by the presence of TGF-beta in culture. This cell line was found to lack high-affinity TGF-beta receptors. The degree of inhibition of B cell proliferation observed in in vitro cultures was found to be dependent not only on the concentration of TGF-beta added but also on the concentration of the growth stimulatory substance (IL 2) present. By increasing the IL 2 concentrations in culture, the inhibition of proliferation induced by TGF-beta could be partially overcome. In contrast, the inhibition of Ig secretion induced by TGF-beta could not be overcome by a higher concentration of stimulatory factor, demonstrating that the suppression of B cell differentiation by TGF-beta is not due solely to its effects on proliferation. Furthermore, it was demonstrated that B lymphocytes secrete TGF-beta. Unactivated tonsillar B cells had detectable amounts of TGF-beta mRNA on Northern blot analysis, and B cell activation with Staphylococcus aureus Cowan (SAC) resulted in a twofold to threefold increase in TGF-beta mRNA. Supernatants conditioned by unactivated B cells had small amounts of TGF-beta, SAC activation of the B cells resulted in a sixfold to sevenfold increase in the amount of TGF-beta present in the supernatants. Thus, B lymphocytes synthesize and secrete TGF-beta and express receptors for TGF-beta. The addition of exogenous TGF-beta to cultures of stimulated B cells inhibits subsequent proliferation and Ig secretion. TGF-beta may function as an autocrine growth inhibitor that limits B lymphocyte proliferation and ultimate differentiation.