title: Identification of a T cell membrane protein possibly involved in IL-4-induced B cell immunoglobulin class switching to IgE.
abstract: The murine T cell hybridoma line, MBI-1.15, secretes a 17-kDa protein which decreases binding activity of the CD23 molecule for its natural ligand, IgE. This protein, denoted epsilon receptor-modulating protein (epsilon RMP), was previously characterized and shown to be a novel serine protease. The present studies show that, in addition to modulating CD23, epsilon RMP costimulates with IL-4 the de novo synthesis and secretion of IgE and IgG 1 by cultured B cells. Since such costimulating activity is reminiscent of a similar synergism with IL-4 previously observed with cell membranes from activated T cells, we examined isolated membranes from the epsilon RMP-producing MBI-1.15 T cell line for comparable activity; indeed, as shown herein, MBI-1.15 cell membranes do exhibit this synergism. Furthermore, we show that a monoclonal antibody (mAb), 2E5B, specific for the 17-kDa soluble form of epsilon RMP, blocks the costimulating activities of both the soluble epsilon RMP and MBI-1.15 T cell membranes for IL-4-induced de novo synthesis of IgE by cultured B cells. This anti-epsilon RMP mAb also detects a 36-kDa membrane-bound protein species which appears to be related to soluble epsilon RMP by immunochemical criteria. The membrane-bound proteins, present on MBI-1.15 T cells, induce germ-line IgE heavy chain transcripts (I epsilon) in I-29 B cells independently of IL-4, and this inductive event is also specifically blocked by the 2E5B anti-epsilon RMP mAb. These findings suggest that T cell membrane-bound epsilon RMP molecules are crucial proteins involved in contact-dependent B cell class switching in the course of IgE biosynthesis. Finally, both IL-4 and epsilon RMP induce I epsilon on I-29 B cells, but neither molecule by itself can induce class switching to IgE synthesis by splenic B cells. This clearly suggests that both epsilon RMP and IL-4 have another important molecular effect (which may or may not be identical) on B cells, that is essential for class switching, but only when both molecules are present simultaneously is the complete mechanism of class switching manifested.
authors.affiliation: Division of Immunology, Medical Biology Institute, La Jolla, California 92037.
authors.forename: S
authors.initials: S
authors.lastname: Matsushita
authors.forename: D H
authors.initials: DH
authors.lastname: Katz
mesh_terms: D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology*; D001667:Binding, Competitive; D005260:Female; D006825:Hybridomas / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014446:Tyrosine 3-Monooxygenase
chemical_list: D048948:14-3-3 Proteins; D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D014446:Tyrosine 3-Monooxygenase; D012697:Serine Endopeptidases