title: Immune dysfunction in mice with plasmacytomas. I. Evidence that transforming growth factor-beta contributes to the altered expression of activation receptors on host B lymphocytes.
abstract: Plasmacytoma-bearing mice (PC-mice) develop a polyclonal B cell immunodeficiency syndrome characterized by marked impairment of: a) primary antibody responses and b) proliferative responses to B cell mitogens. The present investigations used two-color flow cytometry to examine B lymphocytes from the spleens and lymph nodes of PC-mice and found decreased surface membrane expression of surface IgM (sIgM), transferrin receptors (TfR) and IgE FcR (CD23), increased expression of class II MHC, but normal expression of B220, Mel-14, Fc gamma RII, and Fc mu R. These changes were not related to the H chain class or the amount of Ig produced by the plasmacytoma. When cultured with IL-4, B lymphocytes from PC-mice increased their expression of sIgM and class II MHC, but not of CD23. Several findings implicate transforming growth factor-beta 1 (TGF-beta 1) in the mechanism that modulates receptor expression on B lymphocytes in PC-mice: a) ascites fluid from PC-mice contains large quantities of TGF-beta 1; b) supernatants of cultured spleen cells from PC mice contain up to eightfold more TGF-beta than is found with normal spleen cells; c) cloned plasmacytoma cells produce TGF-beta in vitro; and d) the abnormal phenotype of B cells from PC-mice, i.e., decreased CD23, sIgM, and TfR, and increased class II MHC, is induced on normal B cells cultured in the presence of TGF-beta 1. Because sIgM, TfR, class II MHC, and CD23 are molecules that play fundamental roles in the activation of normal B cells, their modulation by TGF-beta 1: a) identifies molecular mechanisms that could account for some of the known immunosuppressive properties of TGF-beta 1 and b) implicates TGF-beta in the pathogenesis of the polyclonal B cell immunodeficiency that is characteristic of plasma cell tumors.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: D J
authors.initials: DJ
authors.lastname: Berg
authors.forename: R G
authors.initials: RG
authors.lastname: Lynch
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000276:immunology*; D011961:Receptors, Fc / Q000096:biosynthesis; D017455:Receptors, IgE; D011990:Receptors, Transferrin / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D011961:Receptors, Fc; D017455:Receptors, IgE; D011990:Receptors, Transferrin; D016212:Transforming Growth Factor beta; D015847:Interleukin-4