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Biomedical subjects

L Flores-Romo

Publications and source records attributed to L Flores-Romo.

At least 37 records · Page 2Linked to original sources
PubMed1993

Inhibition of an in vivo antigen-specific IgE response by antibodies to CD23.

Immunoglobulin E (IgE) mediates many allergic responses. CD23 is a 45-kilodalton type II transmembrane glycoprotein expressed in many cell types. It is a low-affinity IgE receptor and interacts specifically with CD21, thereby modulating IgE production by B lymphocytes in vitro. In an in vivo model of an allergen-specific IgE response, administration of a rabbit polyclonal antibody to recombinant human truncated CD23 resulted in up to 90 percent inhibition of ovalbumin-specific IgE synthesis. Both Fabs and intact IgG inhibited IgE production in vitro and in vivo. Thus, CD23 participates in the regulation of IgE synthesis in vivo and so could be important in allergic disease.

Amino Acid Sequence↗
PubMed1993

A new pair of surface molecules involved in human IgE regulation.

The molecules controlling IgE production are the subject of intense study in the effort to find new ways to treat allergic diseases. One candidate, the CD23 molecule, a low affinity receptor for IgE, was recently identified to interact with another molecule, named CD21, in the regulation of IgE production.

B-Lymphocytes↗
PubMed1993

Receptors for IgE.

Following advances during the past 5 years in our understanding of the molecular structure of receptors for IgE, progress has been made in elucidating the structure and function of IgE receptors and the signalling events through these receptors. IgE is not the only ligand for some of these receptors, leading to their having unexpected and interesting biological activities.

Animals↗
PubMed1993

Anti-CD40 antibody stimulates the VLA-4-dependent adhesion of normal and LFA-1-deficient B cells to endothelium.

We have demonstrated that anti-CD40 antibody stimulates the heterotypic adhesion of B cells to endothelial cells. This has been shown by using normal B lymphocytes and B-cell lines in a quantitative adhesion assay. When B cells, B-cell lines and Epstein-Barr virus (EBV)-transformed B cells from a patient with leucocyte adhesion deficiency (LAD) were stimulated with anti-CD40 antibody, they were found to adhere to both untreated and interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC), and to the lung carcinoma line A549. To identify the adhesion receptors responsible for this anti-CD40-induced adhesion, cells were pretreated with blocking antibodies prior to assay. Our results indicate that anti-CD40-stimulated adhesion of tonsillar B cells, B-cell lines RPMI-8866, JY, and an EBV-transformed LAD-cell line were predominantly dependent on the very late antigen-4 (VLA-4)-vascular cell adhesion molecule (VCAM) interaction. Anti-CD40-induced adhesion appears to be dependent on the activation of protein tyrosine kinase and protein kinase C and on the presence of divalent cations.

Antibodies↗
PubMed1991

Growth factor requirements for the stimulation of germinal center B cells: evidence for an IL-2-dependent pathway of development.

Germinal center (GC) B cells readily undergo apoptosis, a tendency which can be suppressed in vitro by immobilized anti-Ig; mAb to CD40 and soluble CD23 (in synergy with IL-1 alpha) also effect rescue of GC cells from programmed cell death. In the present study, the signals which stimulate rescued GC populations to DNA synthesis have been examined and compared to those established for the activation of follicular mantle (FM) B cells. On co-culture with anti-Ig, optimal responses in FM B cells can be achieved with a combination of IL-4 and CD40 antibody; these activities also provided a modest stimulus to GC cells but, for this population, anti-Ig was ineffective at augmenting the response further. Stimulations of GC B cells were enhanced, however, when performed on a support of primary fetal lung fibroblasts; a major influence of stroma was to promote, by direct cell-cell contact, the CD40-dependent survival of GC B cells. FM B cells were relatively independent of such stromal support. In marked contrast to FM cells, GC B cells were found to respond by enhanced DNA synthesis to IL-2 even when quite low concentrations of the factor were present (IC50 = 2 U/ml). Stimulation of GC cells via this pathway was augmented almost 2-fold on the inclusion of anti-Ig whereas neither fibroblasts, IL-4, nor CD40 antibody made any additional contribution to the IL-2-dependent response. The requirements found for stimulating GC cells in vitro are discussed with reference to the signals that this population may encounter in appropriate microenvironments in vivo: the variety of options apparently available could reflect changing priorities at different stages of a developing GC response.

Antigens, CD↗
PubMed1990

Functional implication for the topographical relationship between MHC class II and the low-affinity IgE receptor: occupancy of CD23 prevents B lymphocytes from stimulating allogeneic mixed lymphocyte responses.

Following the observation of Bonnefoy et al. (J. Exp. Med. 1988. 167:57), that the low-affinity IgE receptor (CD23) on B lymphocytes can be coupled (with the use of chemical cross-linking reagents) to major histocompatibility complex (MHC) class II DR molecules, we now report that ligands binding within the lectin-homology region of CD23 prevent B cells from stimulating allogeneic mixed lymphocyte responses. Ligands capable of blocking mixed lymphocyte responses include the anti-CD23 antibodies MHM6 and EBVCS 4 but not EBVCS 1 and 5. IgE itself, and small peptides representing sequences within the CH3 domain of IgE. The detailed topographical relationship between CD23 and MHC class II on the B lymphocyte surface was examined using dual immuno-fluorescence labeling of cells and direct visualization of the staining by confocal laser scanning microscopy. On transformed B lymphoblasts, the two antigens were seen to co-localize in discrete patches; on normal B cells which had been cultured for 2 days with interleukin 4, CD23 and MHC class II converged at a single pole which exhibited a tendency to pseudopod formation and provided a focus for homotypic cell-cell interactions. The possibility that CD23 could serve as a co-stimulatory-adhesion molecule in antigen presentation by B lymphocytes is discussed with special reference to a potential role in the regulation of IgE synthesis.

Antibodies, Monoclonal↗
PubMed1990

Immunoglobulin isotype production by cycling human B lymphocytes in response to recombinant cytokines and anti-IgM.

Actively cycling populations of purified human tonsilar B lymphocytes were examined for their capacity to secrete IgM, IgA, IgE and IgG of all four subclasses in direct response to recombinant cytokines; in some experiments, monoclonal antibody to IgM (anti-mu) was included in order to explore the influence of antigen receptor ligation on immunoglobulin (Ig) production. Enhanced IgM release was seen on culture of the cycling cells with either interleukin-2 (IL-2), IL-4 or interferon-alpha (IFN-alpha). IL-2 and IFN-alpha also augmented IgA production, whereas IL-4 had no effect on this isotype. IL-4 did, however, encourage the production of the IgG subclasses IgG1, IgG2 and IgG3, while IL-2 augmented IgG1 and IgG3 release and IFN-alpha increased IgG1 levels. IgG4 production, and that of IgE, failed to be perturbed by any of the cytokines assayed. Neither IL-1 alpha, IL-1 beta, IL-5 nor IFN-gamma significantly altered the profile of Ig isotype release. When confronted with anti-mu, cycling B cells demonstrated a marked suppression in IgM production. Suppression could not be overcome by the addition to culture of the normally IgM-promoting IL-4. Concomitant with the reduction in IgM levels, an increase in IgG release was observed. This was comprised of elevations in IgG1 and IgG3. Although not influencing IgA release directly, anti-mu was found to promote increased IgA production in co-culture with either IL-2 or IFN-alpha. The findings are discussed in the context of recent findings on Ig isotype control in both human and murine systems.

Antibodies, Anti-Idiotypic↗
PubMed1989

CD23: a multi-functional receptor/lymphokine?

With the demonstration of identity between CD23 and the low affinity IgE Fc receptor (Fc epsilon RII), two previously separate avenues of immunological research have converged into one. Particularly in its guise as 'Blast-2' antigen, evidence has been mounting to implicate CD23 as an important molecule in B-cell growth regulation. It might seem pertinent, however, to question a role for an apparently isotype-specific immunoglobulin (Ig) receptor in general B-cell processes. In this article, John Gordon and colleagues attempt to reconcile the two, currently diverse, schools of thought regarding the primary function of CD23 and to provide a structural model that accounts for the biological pleiotropy observed.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

B-cell reconstitution after autologous bone marrow transplantation: increase in serum CD23 ("IgE-binding factor") precedes IgE and B-cell regeneration.

The serum levels of IgE and the soluble cleavage product of CD23 (sCD23) were prospectively monitored for up to 1 year after transplantation in 34 patients who underwent autologous (n = 33) or syngeneic (n = 1) bone marrow transplantation (BMT). In 25 patients (74%), a transient IgE peak (two- to 2,750-fold increase) appeared in the serum 3 to 4 weeks after BMT. In 18 patients (51%), a two- to 125-fold increase in sCD23 coincided with the IgE peak. In only three patients was a sCD23 peak observed without a concomitant increase in IgE. The sCD23 increment preceded the IgE peak in each individual case. During the period of increased sCD23 serum levels, the absolute numbers of circulating B cells and other cell types expressing surface CD23 were extremely low. The biologic significance of these findings is discussed in light of present knowledge of regulation of B-cell growth and differentiation with special reference to the role of sCD23 as a multifunctional cytokine.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Regulation of resting and cycling human B lymphocytes via surface IgM and the accessory molecules interleukin-4, CD23 and CD40.

Experiments were designed in order to compare directly the ability of a new and potent monoclonal anti-mu chain antibody to initiate or maintain stimulation in resting and cycling B lymphocytes, respectively. Resting B cells could be stimulated by soluble anti-mu only in the presence of additional signals; these could be supplied by a high dose of phorbol ester or a combination of interleukin-4 (IL-4) and the CD40 antibody, G28-5. Immobilization of anti-mu not only increased the magnitude of the resting B-cell response but also diminished the co-factor requirements. The 'background' stimulation obtained when using a high concentration of immobilized anti-mu was unexpectedly reduced in the presence of IL-4 alone. The duration, but not the magnitude, of the IL-4 signal required for promoting optimal responses varied with the co-stimulation applied. Importantly, the threshold concentrations of soluble anti-mu needed to trigger the resting B cells were reduced upon the addition of each co-stimulant. With actively cycling B cells, both soluble and immobilized anti-mu were now capable of sustaining stimulation which could be prolonged on the addition of IL-4 and/or G28-5. In both resting and cycling populations, a strong correlation was noted between the magnitude of stimulation elicited when IL-4 was present and the release of the soluble CD23 molecule. Moreover, IL-4-promoted, but not other, stimulations could be augmented up to 10-fold by the inclusion of the CD23 antibody MHM6. Both the resting and cycling B-cell populations were found to secrete IgM in direct response to IL-4 and G28-5; this factor-driven production of IgM was differentially modulated by soluble and immobilized anti-mu in the two populations.

Antibodies, Monoclonal↗
PubMed1989

Soluble fragments of the low-affinity IgE receptor (CD23) inhibit the spontaneous migration of U937 monocytic cells: neutralization of MIF-activity by a CD23 antibody.

U937 monocytic cells were found to respond by diminished spontaneous migration when confronted with affinity-purified soluble fragments of the low-affinity receptor for IgE (FcER2/CD23). Unlike B lymphoma cells, U937 cells could not be activated to respond with enhanced DNA synthesis through their membrane-bound CD23 antigen by MHM6, a monoclonal antibody within the CD23 cluster. MHM6 did, however, effectively neutralize the U937-directed MIF (migration inhibition factor) activity contained within the soluble CD23 preparations. The findings not only suggest a role for soluble CD23 as a novel cytokine at sites of inflammation but also indicate different functions for the membrane-bound forms expressed on B cells and monocytes.

Antibodies, Monoclonal↗
PubMed1989

Phorbol ester and calcium ionophore are sufficient to promote cell replication in cultures of quiescent human B lymphocytes.

Highly purified, resting B cells could be induced to grow for up to 10 days by culturing in the presence of a synergistic combination of a tumour-promoting phorbol ester and the calcium ionophore ionomycin. In spite of evident cell death occurring, four to five times as many viable B lymphocytes could be harvested at the end of culture than were initially plated. Soluble factors derived from T cells (interleukin-2, commercial B-cell growth factor) or monocytes (interleukin-1) failed to augment further the growth-promotion observed. Evidence is presented to suggest that an autocrine component might be necessary for maintenance of the cell-cycle and growth initiated by the phorbol ester and calcium ionophore combination. The significance of these findings to B-cell physiology are discussed.

B-Lymphocytes↗
PubMed1988

Soluble CD23 is released by B lymphocytes cycling in response to interleukin 4 and anti-Bp50 (CDw40).

An enzyme-linked immunoassay was developed to quantitate the production of soluble CD23 from cycling B lymphocytes. This molecule has identity both with B cell-derived B cell growth factor and with an IgE-binding factor. B lymphocytes, which had been stimulated for 3 days with phorbol dibutyrate and calcium ionophore, washed and recultured, failed to produce detectable levels of CD23 over the following 3 days. Soluble CD23 was found, however, in the supernatant of cultures where recombinant interleukin 4 had been included. The level of CD23 rose dramatically when anti-Bp50 had also been added. By contrast, anti-Bp50, alone or together with low molecular weight T cell-derived B cell growth factor, failed to promote the release of CD23 in detectable amounts. There was a strong correlation between the appearance of soluble CD23 in culture supernatants and the expression of CD23 on the surface of restimulated cells. The level of CD23 release appeared to relate more to the continued cycling of cells than to their differentiation to immunoglobulin secretion. These findings are discussed with particular emphasis on the role of CD23 as an important multi-functional lymphokine in B lymphocyte physiology.

B-Lymphocytes↗
PubMed1988

The marmoset B-lymphoblastoid cell line (B95-8) produces and responds to B-cell growth and differentiation factors: role of shed CD23 (sCD23).

The EBV-producing marmoset B-cell line (B95-8), commonly used as a source of EBV for stimulation and transformation of human B cells, was shown to proliferate in response to supernatants containing human B-cell growth factors (BCGF) derived from PHA-activated T cells or the KG-la cell line, and to a commercial low molecular weight BCGF (BCGFlow), but not to recombinant human IL-4 (rhIL-4). In this respect, B95-8 responded in much the same way as human EBV-transformed lymphoblastoid cell lines (LCL). In contrast, B95-8 did not secrete immunoglobulin in response to B-cell differentiation factor (BCDF) containing supernatants from the KG-la cell line, nor to BCGFlow, or IL-6 obtained from the T24 bladder carcinoma cell line, whereas significant responses were obtained with human EBV-transformed LCL. Both B95-8 and control EBV-transformed human LCL secreted BCGF and BCDF detected with the indicator B-cell lines CESS, L4, and HFB1, but only the human LCL secreted BCGF detectable in co-stimulation assays with TPA-activated tonsillar B cells. Unlike EBV-transformed LCL, B95-8 did not express detectable surface CD23, and did not release into the culture medium soluble CD23 (sCD23) recognized by an EIA for the human molecule. Although not releasing detectable sCD23, B95-8 cells did proliferate in response to purified human sCD23, and were found to be 1000 times more sensitive in this assay than EBV-transformed LCL. This may provide a basis for a sensitive bioassay for sCD23. Unlike EBV-transformed LCL, it seems that in vitro proliferation of B95-8 may involve an autocrine loop which does not depend on CD23.

Animals↗