RESUMEN
In comparison to B cell stimulation mediated by surface immunoglobulin (Ig) antigen receptor ligation, little is known about the intracellular events associated with T cell-dependent B cell responses. A model for the efferent phase of T cell-B cell interaction was used to examine the capacity of activated T cells to trigger nuclear expression of the trans-acting transcription factor, NF-kappa B, in B cells. Fixed, activated, but not fixed, resting Th2 cells were found to induce increased binding activity for a kappa B site-containing oligonucleotide in a time-dependent manner. This induction of NF-kappa B was eliminated by an antibody directed against a 39-kD cell interaction protein on activated T cells as well as by a soluble form of B cell CD40. Of particular relevance to intracellular signaling, NF-kappa B induction was not diminished by prior depletion of B cell protein kinase C (PKC) with phorbol myristate acetate. These results strongly suggest that T cell-dependent B cell stimulation is associated with NF-kappa B induction via p39-CD40 interaction and that this is brought about by non-PKC dependent signaling, in marked contrast to the previously documented requirement for PKC in sIg receptor-mediated stimulation. This suggest that NF-kappa B responds to more than one receptor-mediated intracellular signaling pathway in B cells and may be part of a "final common pathway" for B cell stimulation.
Asunto(s)
Linfocitos B/metabolismo , FN-kappa B/biosíntesis , Linfocitos T/fisiología , Animales , Linfocitos B/inmunología , Secuencia de Bases , Línea Celular , ADN , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia MolecularRESUMEN
The ability of syncytiotrophoblast plasma membrane lipid and protein fractions (STPM lipids, STPM proteins), tested under a reconstituted form, to inhibit lymphocyte proliferation induced by PHA was investigated. The cytostatic activity of STPM proteins appeared greater than that of the STPM lipids. Furthermore, IL-2 production and IL-2 receptor expression by activated lymphocytes were markedly decreased in the presence of STPM proteins compared to the native membrane but remained unaffected in the presence of STPM lipids. Finally, the inhibition of lymphoproliferation could be maintained after removal of the protein fraction from lymphocytes prior to stimulation by PHA. The biological and immunological significance of these results is discussed.
Asunto(s)
Linfocitos/efectos de los fármacos , Proteínas de la Membrana/farmacología , Embarazo/metabolismo , Trofoblastos/metabolismo , División Celular/efectos de los fármacos , Membrana Celular/metabolismo , Regulación hacia Abajo , Femenino , Humanos , Interleucina-2/metabolismo , Linfocitos/metabolismo , Fitohemaglutininas , Receptores de Interleucina-2/efectos de los fármacosRESUMEN
PROBLEM: The aim of this work was to define the respective responsibilities of the lipid and protein components of syncytiotrophoblast plasma membranes on the inhibition of lymphocyte proliferation induced in vitro. METHOD: A fractionation method using octyl-beta-D-glucopyranoside enabled lipoprotein, lipid, and protein fractions to be isolated from the membrane. RESULTS: The lipid fraction was shown nonspecifically to inhibit lymphocyte proliferation, to a lower extent compared with the native membrane. Alternatively, the protein fraction used as a proteoliposome contained the totality of the cytostatic effect of the native fraction. CONCLUSION: These results are discussed generally in the context of the immunoregulatory role of membrane lipids and proteins and in relation to the local properties of syncytiotrophoblast plasma membrane components in fetal graft tolerance.