Distinct effect of forskolin and interferon-γ on cell proliferation and regulation of histocompatibility antigen expression in hematopoietic cells

The B cell receptor (BCR) triggers a variety of biological responses that differ depending upon the properties of the antigen. A panel of M13 phage-displayed peptide ligands with varying affinity for the 3-83 antibody was generated to explore the role of antigen-BCR affinity in cell activation studies using primary 3-83 transgenic mouse B cells. Multiple parameters of activation were measured. T cell–independent B cell proliferation, antibody secretion, induction of germline immunoglobulin γ1 transcripts, and B cell production of interleukin (IL) 2 and interferon γ responses were better correlated with antigen-BCR affinity than with receptor occupancy. In contrast, other responses, such as upregulation of major histocompatibility complex class II and B7.2 (CD86), secretion of IL-6, and B cell proliferation in the context of CD40 signaling were only weakly dependent on antigen affinity. Biochemical analysis revealed that at saturating ligand concentrations the ability of phage to stimulate some early signaling responses, such as Ca++ mobilization and tyrosine phosphorylation of syk or Igα, was highly affinity dependent, whereas the ability to stimulate Lyn phosphorylation was less so. These data suggest that the BCR is capable of differential signaling. The possibility that differential BCR signaling by antigen determines whether an antibody response will be T independent or dependent is discussed.

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Selection of Vδ+ T Cell Receptors of Intestinal Intraepithelial Lymphocytes is Dependent on Class II Histocompatibility Antigen Expression

Function and Specificity of γ/δ T Cells - Current Topics in Microbiology and Immunology ◽

10.1007/978-3-642-76492-9_36 ◽

1991 ◽

pp. 255-267 ◽

Cited By ~ 2

Author(s):

L. Lefrancois ◽

R. LeCorre ◽

Judy Mayo ◽

J. A. Bluestone ◽

T. Goodman

Keyword(s):

T Cell ◽

T Cell Receptors ◽

Antigen Expression ◽

Class Ii ◽

Intraepithelial Lymphocytes ◽

Histocompatibility Antigen ◽

Cell Receptors ◽

Intestinal Intraepithelial Lymphocytes ◽

Selection Of

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Regulation of human monocyte HLA-DR and CD4 antigen expression, and antigen presentation by 1,25-dihydroxyvitamin D3

Blood ◽

10.1182/blood.v76.1.189.189 ◽

1990 ◽

Vol 76 (1) ◽

pp. 189-197 ◽

Cited By ~ 85

Author(s):

WF Rigby ◽

M Waugh ◽

RF Graziano

Keyword(s):

Cell Proliferation ◽

T Cell ◽

Antigen Presentation ◽

Antigen Expression ◽

Human Monocyte ◽

T Cell Proliferation ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

Hla Dr ◽

And Function

Abstract 1,25-Dihydroxyvitamin D3 (1,25(OH)2-D) has been shown to be a macrophage-derived cytokine, capable of regulating myeloid differentiation and T-cell activation in vitro. Therefore, we examined the effects of 1,25(OH)2-D on the monocyte phenotype and function of human peripheral blood monocytes as an index of its biologic role at an inflammatory site. 1,25(OH)2-D treatment consistently and specifically reduced HLA-DR and CD4 expression by monocytes, while CD14 and class I HLA antigen expression were unaffected. Expression of Fc gamma R I-III on monocytes was variably modulated by 1,25(OH)2-D treatment, but no differences in antibody-dependent cell cytotoxicity (ADCC) were observed, measured using either ADCC or anti-Fc gamma R-antibody expressing hybridomas. In contrast, the ability of monocytes to induce antigen-dependent T-cell proliferation was markedly reduced by 1,25(OH)2-D pretreatment for as little as 6 hours. Addition of interleukin-1 (IL-1), IL-6, or indomethacin did not restore antigen- dependent T-cell proliferation, suggesting that this observation was not secondary to changes in IL-1, IL-6, or PGE2 production induced by 1,25(OH)2-D. These data suggest that 1,25(OH)2-D treatment specifically modulates human monocyte phenotype and function, altering HLA-DR antigen expression and antigen presentation, while leaving lytic function intact. These findings may be relevant to the immunobiologic role of 1,25(OH)2-D.

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Fas/APO-1 (CD95)–Mediated Apoptosis Is Activated by Interferon-γ and Interferon- in Interleukin-6 (IL-6)–Dependent and IL-6–Independent Multiple Myeloma Cell Lines

Blood ◽

10.1182/blood.v92.8.2914 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2914-2923 ◽

Cited By ~ 54

Author(s):

Helena Spets ◽

Patrik Georgii-Hemming ◽

Jan Siljason ◽

Kenneth Nilsson ◽

Helena Jernberg-Wiklund

Keyword(s):

Multiple Myeloma ◽

Cell Lines ◽

Poor Response ◽

Antigen Expression ◽

Myeloma Cell ◽

Interferon Γ ◽

Dependent Manner ◽

Multiple Myeloma Cell ◽

Ifn Γ ◽

Induced Apoptosis

Abstract A poor response to Fas-induced apoptosis is evident in some multiple myeloma (MM) cell lines and primary cells. In this study, we have examined the possibility to increase the sensitivity to Fas-induced apoptosis by pretreatment of MM cells with interferon-γ (IFN-γ) or interferon- (IFN-). Both IFN-γ and IFN- markedly increased the Fas-induced apoptosis in all cell lines tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-1958 cell lines, pretreatment with either IFN-γ or IFN- also inhibited proliferation in a dose-dependent manner. In contrast, IFN-γ activation of the Fas death pathway in the U-266-1984 cells was not accompanied by growth inhibition. Incubation with the IFNs increased the Fas antigen expression in one of three cell lines but did not alter the expression of Bcl-2 or Bax. The IFNs are important regulators of growth and survival in MM cells. Our results suggest that activation of Fas-mediated apoptosis is a novel mechanism by which the IFNs exert inhibitory effects on MM cells. © 1998 by The American Society of Hematology.

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