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P del Guercio

Publications and source records attributed to P del Guercio.

17 recordsLinked to original sources
PubMed1993

Expression of conformationally constrained adhesion peptide in an antibody CDR loop and inhibition of natural killer cell cytotoxic activity by an antibody antigenized with the RGD motif.

We report that an antibody engineered to express three Arg-Gly-Asp (RGD) repeats in the third complementarity-determining region of the heavy chain (antigenized antibody) efficiently inhibits the lysis of human erythroleukemia K-562 cells by natural killer (NK) cells. Synthetic peptides containing RGD did not inhibit. Inhibition was specific for the (RGD)3-containing loop and required simultaneous occupancy of the Fc receptor (CD16) on effector cells. The antigenized antibody inhibited other forms of cytotoxicity mediated by NK cells but not cytotoxicity mediated by major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL). A three-dimensional model of the engineered antibody loop shows the structure and physicochemical characteristics probably required for the ligand activity. The results indicate that an RGD motif is involved in the productive interaction between NK and target cells. Moreover, they show that peptide expression in the hypervariable loops of an antibody molecule is an efficient procedure for stabilizing oligopeptides within a limited spectrum of tertiary structures. This is a new approach towards imparting ligand properties to antibody molecules and can be used to study the biological function and specificity of short peptide motifs, including those involved in cell adhesion.

Amino Acid Sequence↗
PubMed1993

The self and the nonself: immunorecognition and immunologic functions.

For almost a century self-nonself discrimination has been considered the driving force of the immune system and the dogma of self-tolerance (horror autotoxicus) the essential issue for understanding protective immunity and pathologic autoreactivity. This classical picture has been recently challenged by the discovery that the immune system is influenced by internal activation (amor autocognitus) and autoreactive clones are both present and activated in healthy individuals. Central to the concepts of reactivity and tolerance, in other terms, to physiology and pathology, is the analysis of structures involved in immunorecognition and as they contribute to the outcome of the immune response. The capacity of the immune system to recognize nonself structures and eventually react to them developed during evolution probably before the generation of clonally distributed antigen receptors. The high level of autoreactivity that characterizes the immune system seems to suggest that immunocompetent cells never learned to ignore the self, but rather that, sometime during evolution, they specialized in the function of self-identification, one of the most basic activities of all living cells. Autoimmune diseases would result from a pathologic deviation of a physiologic function, just as many other diseases do.

Animals↗
PubMed1987

Inhibitory activity of interleukin B on the suppressor T cell hybrid T2D4.

Interleukin B (IL-B), a product of unstimulated B cells, is defined by its ability to selectively prevent the differentiation of suppressor T lymphocytes from precursors into effectors. The present study was undertaken to determine whether IL-B could also be active in modulating the activity of the T cell hybrid T2D4, which produces immunoglobulin-binding suppressor factors. T2D4 cells can be selectively induced by incubation with various isotypes of antibody to express isotype-specific Fc receptors and to release soluble factors that suppress production of the corresponding isotype. The data presented here demonstrate that IL-B is greatly effective in inhibiting T2D4 activities. Either pretreatment with IL-B or continuous exposure to IL-B prevents isotype activation of T2D4. As a result, T2D4 cells do not express isotype receptors and do not produce detectable amounts of isotype-specific suppressor factors. This IL-B regulatory activity on T2D4 is temperature dependent and is inhibited by cytochalasin B. These findings provide new insights on the mechanism by which IL-B enhances antibody responses, and they offer a conceptual framework for analyzing IL-B activity on suppressor T cells.

Animals↗
PubMed1986

B-cell-derived lymphokines: regulatory effects on the immune system.

While both regulatory and effector functions within the T cell lineage have been extensively studied, B lymphocytes have been considered merely a source of humoral antibodies until recently. With the exception of antibody feedback, only a limited number of investigations have been designed to explore the possibility that B cells may exert regulatory activity. The purpose of this review is to analyze how B cells can modulate themselves by generating signals (lymphokines), which under certain circumstances may initiate a chain of regulatory events. Only factors exclusively produced by B cells are considered. While, for the most part, this review is dedicated to recent studies on nonimmunoglobulin B cell factors, the role played by Ig molecules as immunoregulatory linker molecules, independently of their antigenic specificity, will be briefly examined. Furthermore, some basic questions regarding the biological significance of these regulatory mechanisms will be raised.

Animals↗
PubMed1985

Regulatory function of Thy-1-negative cells: V. A lymphokine of B cell origin (BEF) induces in vitro high antibody response in genetically selected low responder mice.

Studies were conducted on two lines of mice genetically selected, respectively, for high (AB/H) and low (AB/L) antibody production, in order to identify the mechanism by which genes involved in the selection express their functions. It was found that B cell-derived enhancing factor (BEF), a lymphokine of B cell origin which acts on T cells by preventing the activation of suppressor cells, is effective in inducing high responses in low responder mice, whereas it is ineffective in modulating antibody production in high responder mice. As a result, no difference was found between the responses of AB/H and AB/L mice when spleen cells were stimulated in vitro in the presence of BEF. AB/H and AB/L mice do not seem to differ in their B cell functions since no difference was found in the capacity of B cells of either line to synthesize antibodies in the presence of T cell-replacing factor (TRF), or to produce endogenous BEF. These data indicate that, at least in vitro, the character of general responsiveness of these two mouse lines mainly reflects differential reactivity of T suppressor cells. Since the two lines represent, respectively, the maximal and minimal responsiveness of an outbred population of animals, it is suggested that the individual difference in antibody response is related to individual differences of T suppressor cells in responding to the immunogen.

Animals↗
PubMed1985

B lymphocyte regulation of the immune system. II. Inhibition of Fc receptor expression of lymphocytes by BEF, a lymphokine of B cell origin.

Recently, we described a new lymphokine of B cell origin, capable of selectively preventing the differentiation of T suppressor cells from the precursor into the effector stage. As a result, antibody production against various antigens is markedly increased. We termed this lymphokine B cell-derived enhancing factor (BEF). To discern the mechanism(s) by which BEF interferes with the activation of T suppressor cells, experiments were undertaken to explore the effect of BEF on the induction of Fc receptors (FcR). The induction of FcR on T cells has been implicated in the down-regulation of antibody synthesis, and it has been suggested that the expression of FcR for a given immunoglobulin precedes the release of factors with regulatory functions for the corresponding isotype. In the experiments reported here, murine spleen cells were incubated for 24 hr in the presence of IgG1 or IgA monoclonal antibodies, were washed, and the number of FcR gamma 1+ and FcR alpha+ cells were calculated by a rosette assay. The effect of BEF was studied either during the inductive phase or before, i.e., by pretreating the cells with BEF for 18 hr at 37 degrees C before the inductive phase. Our results show that BEF abolishes, in a dose-dependent manner, the expression of isotype-specific FcR in spleen cells when present during the inductive phase, as well as when cells are pretreated with it. In successive experiments, we tested the effect of BEF on the induction of FcR on T cell-enriched or B cell-enriched spleen cells. The results show that BEF is effective in selectively inhibiting FcR expression on T lymphocytes, but not on B lymphocytes, once isolated from the total spleen cell population. These findings provide further insight into the mechanism by which BEF modulates the immune response, and suggest that different mechanisms may be involved in the induction of FcR on T and B lymphocytes, respectively.

Animals↗
PubMed1985

B lymphocyte regulation of the immune system. I. In vivo biologic activity of the novel lymphokine, B cell-derived enhancing factor (BEF).

B cell-derived enhancing factor (BEF) is a lymphokine of B cell origin which was originally identified and characterized by its ability to enhance in vitro antibody responses, an effect shown to be due to the ability of BEF to reduce the activation of suppressor T cells. The present study was undertaken to determine whether BEF could also be active in modulating antibody responses in vivo. The data presented here demonstrate that BEF is biologically active in vivo, as manifested by significantly enhanced primary IgM and IgG antibody responses in mice that were either injected with BEF prepared exogenously or implanted with growing BEF-secreting cells of a B cell line. Moreover, BEF was shown to enhance subsequent development of immunologic memory in mice pretreated with BEF at the time of primary immunization; these mice then displayed enhanced secondary responses when challenged with the same antigen some weeks later. The mechanism by which BEF exerts biologic activities to positively modulate in vivo antibody responses and immunologic memory reflects the ability of BEF to modulate one or more T cell functions, as evidenced by the following findings. 1) Transient in vitro exposure to BEF of T cells, but not of B cells, endowed such cells with the capacity to adoptively transfer enhanced primary antibody responses to irradiated recipients. 2) Utilizing adoptive in vivo antibody responses, in which fractionated B cell or T cell populations were obtained from BEF-pretreated mice, revealed that one effect of BEF which results in enhanced immunologic memory is related to its activity on T cells during the priming phase of the immune response. Finally, the existence of this B cell-derived lymphokine and the demonstration of its in vivo regulatory effects on the immune system provide yet another example of the emerging biologic importance of B lymphocytes in the overall regulation of the immune system.

Animals↗
PubMed1983

Regulatory function of Thy-1- cells. IV. Biologic and Biochemical characterization of B cell clone-derived lymphokine (BEF).

Studies were made on the immunoregulatory activity of a lymphokine produced by a B cell clone that does not express immunoglobulin heavy or light chains. The B factor (BEF; B cell-derived enhancing factor), was effective in augmenting the primary and the anamnestic response to SRBC and/or in prolonging the IgG anamnestic response to SRBC and the response to DNP-LE, provided it was added at early stages of culture. The BEF seems to act mainly by preventing the activation of T suppressor cells rather than by counteracting the activity of already activated suppressor cells. Indeed, thymocytes and virgin T cells, but not Con A-activated thymocytes, Con A-activated T cells or B cells, express acceptors for the BEF. The biochemical properties of the BEF were also reported. The apparent m.w. of the factor was 450,000 to 500,000 by gel chromatography. The BEF was sensitive to digestion by papain, trypsin, and subtilisin, indicating that it was protein in nature. The regulatory activity was precipitated by 50% (NH4)2SO4 and was destroyed by heating at 70 degrees C for 30 min or by exposure to pH 2.2 for 6 hr.

Animals↗
PubMedDate not supplied

Characterization of murine interleukin B by a monoclonal antibody.

Interleukin B (IL-B), formerly termed BEF (B-cell-derived enhancing factor) or IL-B4, was originally described as a non-immunoglobulin regulatory factor spontaneously produced by B lymphocytes and B-cell lines that enhances the in vitro antigen-driven antibody response of unfractionated spleen cells stimulated by thymus-dependent antigens. Since then we have examined the function of interleukin B in a number of immune reactions, both in vitro and in vivo, and found that it inhibits the activation of suppressor T lymphocytes. We report here the production of two monoclonal antibodies (mAb) that specifically inhibit interleukin B activity. The use of these mAb in the purification and characterization of IL-B is described. IL-B from both normal and transformed B cells consists of two subunits of similar size and amino-acid composition. The structure of interleukin B and its specific behaviour in biological assay distinguish it from many other known lymphokines.

Animals↗
PubMedDate not supplied

Immune response in mice and lack of response in guinea-pigs and in rabbits to DNP on polysaccharide.

The immunogenicity of three DNP-LE conjugates possessing different numbers of haptenic determinants per molecule of carrier (DNP 3-LE, DNP6-LE, DNP 13-LE) has been tested in mice. All conjugates induce only 19S anti-DNP antibodies, but the lowest conjugate is more immunogenic. Lack of response to DNP-LE is observed in guinea-pigs and in rabbits, animals in which native LE is not immunogenic. The immune response is not affected in mice tolerant to LE, when immunization is performed intravenously. These results are discussed with a view to determine the role played by a T-independent carrier in the antibody synthesis against a hapten.

Animals↗