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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
Journal article   Peer reviewed

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

Daniel J Berg and Richard G Lynch
The Journal of immunology (1950), Vol.146(8), pp.2865-2872
04/15/1991
DOI: 10.4049/jimmunol.146.8.2865
PMID: 1826699

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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.
Flow Cytometry Receptors, Transferrin - biosynthesis Gene Expression Regulation Transforming Growth Factor beta - physiology Histocompatibility Antigens Class II - biosynthesis Plasmacytoma - immunology Interleukin-4 - pharmacology Animals B-Lymphocytes - immunology Receptors, Fc - biosynthesis Receptors, IgE Antigens, Differentiation, B-Lymphocyte - biosynthesis Fluorescent Antibody Technique Female Mice Mice, Inbred BALB C B-Lymphocytes - metabolism Immunoglobulin M - biosynthesis

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