title: Further studies of the role of transforming growth factor-beta in human B cell function.
abstract: This study was designed to address three specific questions in human B cells. First, to determine whether transforming growth factor-beta (TGF-beta)2 has similar biologic effects on B cell function as does TGF-beta 1. Second, to test the hypothesis that TGF-beta 1 is an autocrine growth and differentiation inhibitor. Finally, because multiple receptor species for TGF-beta have been identified on other cell types, to determine by chemical cross-linking and competitive binding studies the nature of the TGF-beta 1 R present on normal and transformed B cells. Exogenous TGF-beta 2 was found to be functionally similar to TGF-beta 1 in its inhibition of factor dependent normal B cell proliferation and Ig secretion. When an antibody, specific for the active form of TGF-beta 1, was added in conjunction with IL-2 to previously stimulated B cell cultures, there was a 14.4 +/- 4.2% increase in B cell proliferation, a 22 +/- 6% increase in IgG production, and a 33 +/- 8.6% increase in IgM production when compared to control cultures. Chemical cross-linking of 125I-TGF-beta 1 to normal B cell membranes identified two major cross-linked species of 65 and 90 kDa. A fivefold excess of unlabeled TGF-beta 1 competitively inhibited the detection of both of these bands while a 50-fold excess of unlabeled TGF-beta 2 did not inhibit the 90-kDa band and only partially inhibited (60%) of the 65-kDa band. Chemical cross-linking of 125I-TGF-beta 1 to transformed B cell membranes identified only a single band of 60 kDa. Scatchard plot analysis of 125I-TGF-beta 1 binding to normal B cells that was competitively inhibited with increasing concentrations of unlabeled TGF-beta 1 revealed both high and low affinity binding sites whereas analysis of 125I-TGF-beta 1 binding in the presence of increasing concentrations of unlabeled TGF-beta 2 revealed only low affinity sites. These findings demonstrate that TGF-beta 2 is as effective as TGF-beta 1 in inhibiting human B cell function, that small amounts of active TGF-beta 1 are present endogenously in in vitro cultures which partially inhibit B cell function, that two major TGF-beta 1 R cross-linked complexes of 65 and 90 kDa are present on normal B cells, and that transformation of B cells may be accompanied by changes in the TGF-beta 1 R.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
authors.forename: J H
authors.initials: JH
authors.lastname: Kehrl
authors.forename: A S
authors.initials: AS
authors.lastname: Taylor
authors.forename: G A
authors.initials: GA
authors.lastname: Delsing
authors.forename: A B
authors.initials: AB
authors.lastname: Roberts
authors.forename: M B
authors.initials: MB
authors.lastname: Sporn
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002648:Child; D002675:Child, Preschool; D003432:Cross-Linking Reagents; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D000906:Antibodies; D003432:Cross-Linking Reagents; D006131:Growth Inhibitors; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors