concanavalin-a and Hypergammaglobulinemia

A case of chronic lymphoproliferative disorder is presented, wherein a morphologically homogeneous population of lymphoid cells displayed properties similar to those described for large granular lymphocytes (LGL). Besides their LGL-like phenotype (VEP 13+, OKM 1+, OKT 10+ Fc-IgG-receptor+, OKT 3-), the proliferating cells were cytotoxic to NK targets as well as to antibody-coated target cells. Clinically, our patient presented low-grade lymphocytosis, splenomegaly, neutropenia, hyperimmunoglobulinemia and recurrent infections. Based upon this and 32 similar cases reported in the literature, we conclude that lympho-proliferative disorders involving GL encompass a variety of clinical entities, ranging from reactive GL lymphocytoses to overt lymphocytic malignancies.

Topics: Adult; Aged; Antibodies, Monoclonal; Bone Marrow; Concanavalin A; Female; Humans; Hypergammaglobulinemia; Isoantigens; Killer Cells, Natural; Leukemia; Lymphocyte Activation; Lymphocytes; Lymphocytosis; Male; Microscopy, Electron; Middle Aged; Neutropenia; Phenotype; Phytohemagglutinins; Receptors, Fc; Receptors, IgG

We examined T-cell proliferation in five patients with X-linked hyper-IgM syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired antigen-induced proliferation, whereas their lectin responses were normal. Thus, in addition to severely depressed antibody responses, patients with XHIM have a defect in antigen-specific T-cell proliferation, which may explain their susceptibility to pathogens such as Pneumocystis carinii.

Topics: Antigens; Antigens, Fungal; Candida; CD40 Antigens; Concanavalin A; Cryptosporidiosis; Diphtheria Toxoid; Disease Susceptibility; Genetic Linkage; Humans; Hypergammaglobulinemia; Immunoglobulin M; Immunologic Deficiency Syndromes; Lectins; Ligands; Lymphocyte Activation; Male; Phytohemagglutinins; Pneumonia, Pneumocystis; Pokeweed Mitogens; T-Lymphocytes; Tetanus Toxoid; X Chromosome

Crossed affinoimmunoelectrophoresis using concanavalin A and Aleuria aurantia lectin as diantennary glycan- and fucose-specific affinocomponents, respectively, was applied to study changes in the concentration and glycosylation of the acute phase protein alpha 1-acid glycoprotein (AGP) in sera obtained from patients with hyperimmunoglobulinemia D and periodic fever syndrome. Increases in concentration of AGP compared to control values were found not only during attacks, but also during remissions. Compared to healthy controls, the presence of diantennary glycan-containing glycoforms of AGP also increased during febrile attacks, while no changes were found during remissions. A continuous high degree of alpha 1-->3 fucosylation was accompanied by a continuous high expression of sialyl Lewisx on AGP. Despite the clinical picture of recurrent febrile attacks with asymptomatic intervals, these studies indicate that hyperimmunoglobulinemia D should be considered a condition of persistent inflammation.

Topics: Adolescent; Adult; Aged; C-Reactive Protein; Carbohydrate Sequence; Concanavalin A; Familial Mediterranean Fever; Female; Fever; Glycosylation; Humans; Hypergammaglobulinemia; Immunoglobulin D; Inflammation; Lectins; Lewis Blood Group Antigens; Male; Middle Aged; Molecular Sequence Data; Orosomucoid

Affinity-purified IgE-binding factors from the plasma of patients with the hyper IgE syndrome (HIE) were assessed for their capacity to enhance IgE synthesis by B cells derived from patients with allergic rhinitis or normal nonatopic donors. IgE-binding factors from three of four HIE patients enhanced IgE synthesis by B cells from patients with perennial allergic rhinitis, or with seasonal allergic rhinitis (SAR) and recent pollen exposure, but did not enhance IgE synthesis by B cells from nonatopic donors or from SAR patients with no recent pollen exposure. IgG synthesis was not affected by HIE IgE binding factors. In contrast, IgE binding factors from three of three nonatopic donors failed to enhance IgE or IgG synthesis. Plasma IgE-binding factors from the fourth patient with HIE contained a mixture of IgE-potentiating activity and IgE-suppressive activity. These two activities could be separated on concanavalin A Sepharose or peanut agglutinin agarose columns. Human IgE potentiating factor, but not IgE suppressive factor, had affinity for concanavalin A but not peanut agglutinin and fractionated into two peaks on gel filtration over Sephadex G-75: one peak with a molecular size of approximately 15,000 D and the other with a molecular size of approximately 60,000 D. The isolation of functional IgE binding factors which potentiate IgE synthesis from the plasma of patients with HIE suggests that IgE-binding factors play an important role in the in vivo regulation of IgE synthesis in man.

Topics: B-Lymphocytes; Concanavalin A; Humans; Hypergammaglobulinemia; Immunoglobulin E; Lectins; Lymphokines; Molecular Weight; Peanut Agglutinin; Prostatic Secretory Proteins; Rhinitis, Allergic, Seasonal

Studies were carried out on the mechanisms by which B lymphocytes are polyclonally activated to secrete antibodies during visceral leishmaniasis. Crude extracts of Leishmania donovani, the aetiological agent of this disease, of Leishmania mexicana amazonensis, the etiological agent of cutaneous leishmaniasis, and of Herpetomonas muscarum, a related non-pathogenic organism, all contain components which cause strong in vitro polyclonal activation of hamster spleen cells leading to the production of antibodies. However, in vivo, only hamsters infected with L. donovani develop hypergammaglobulinaemia due to B cell polyclonal activation. Hamsters injected with the crude extracts of leishmania or infected with L. mexicana amazonensis do not manifest these alterations in their B cell response. Furthermore spleen cells of hamsters infected with L. donovani became unresponsive to stimulation with the T cell mitogen phytohaemagglutinin (PHA) by day 10 of infection, whereas their response to concanavalin A (Con A) was preserved. The decreased lymphocyte response to PHA coincided with the augmentation of the PFC/spleen ratio. In contrast, spleen cells from hamsters infected with L. mexicana amazonensis, responded normally to both mitogens throughout the course of infection. These results suggest that the hypergammaglobulinaemia present in visceral leishmaniasis may be the consequence of an inbalance of regulatory T cells, possibly associated with a direct stimulation of hamster B cells by L. donovani components.

Topics: Animals; Antibody Formation; B-Lymphocytes; Concanavalin A; Cricetinae; Female; Hypergammaglobulinemia; Leishmaniasis, Visceral; Male; Mitosis; Phytohemagglutinins; Spleen; T-Lymphocytes; Time Factors; Trypanosoma

The status of suppressor T cells (Ts) was assessed in seven children with the hyper IgE syndrome (recurrent staphylococcal infections, eczematous skin rash, and elevated serum IgE) to determine whether a deficiency in Ts is associated with increased IgE synthesis. When circulating T cells and their subsets were enumerated with the aid of monoclonal antibodies that identify T cells (T3), helper/inducer T cells (T4), and suppressor/cytotoxic T cells (T8), there was a selective deficiency of T3+ cells (51.7+/-11.2% vs. 66+/-5% for normal controls) and of T8+ cells (7.5+/-4.4% vs. 22+/-4% for normal controls) but not of T4+ cells (36.5+/-7.5% vs. 37+/-3% for normal controls). Suppressor T cell function was assessed by examining the ability of mononuclear cells incubated for 48 h with concanavalin A to suppress the proliferation of fresh autologous mononuclear cells in response to the mitogens phytohemagglutinin and pokeweed mitogen. All seven patients were severely deficient in concanavalin A-inducible suppressor cells. In vitro de novo synthesis of IgE in 6-d cultures of peripheral blood lymphocytes was measured in four patients by a solid-phase radioimmunoassay. Mononuclear cells from all four patients synthesized spontaneously increased quantities of IgE in vitro (4,950+/-3,760 pg/10(6) cells vs. 250+/-215 pg/10(6) cells for eight normal controls). IgE synthesis was suppressed by the addition of parental T cells to the culture. Elimination of the T8+ subset, but not of the T4+ subset, by complement-dependent lysis resulted in the loss of the capacity of parental T cells to suppress IgE synthesis. These results suggest that a deficiency of Ts underlies the elevated IgE levels observed in the hyper IgE syndrome.

Topics: Adult; Antibodies, Bacterial; Antigens, Bacterial; Child; Child, Preschool; Concanavalin A; Female; Humans; Hypergammaglobulinemia; Immune Tolerance; Immunoglobulin E; Male; Staphylococcus aureus; Syndrome; T-Lymphocytes, Regulatory

Topics: Child; Concanavalin A; Humans; Hypergammaglobulinemia; Immunity; Immunoglobulin E; Lymphocyte Activation; Male; Phagocytosis; Phytohemagglutinins; Pokeweed Mitogens; Syndrome

Bone marrow mononuclear cell populations were studied in 35 patients without myeloma, 39 patients with multiple myeloma, and 15 patients with benign monoclonal gammopathy. Bone marrow mononuclear cell receptors, responses to mitogens or allogeneic stimuli, and suppressive effects on in vitro peripheral blood lymphocyte (PBL) function were studied. In bone marrow cell populations from patients with untreated multiple myeloma, the percent of complement receptor-bearing cells and the pokeweed mitogen- and concanavalin A-stimulated responses were significantly greater than were those in bone marrow cell populations from patients without myeloma. Sheep red blood cell receptor-bearing cells were significantly greater in marrow populations from treated multiple myeloma patients compared to those from untreated multiple myeloma patients. Sheep red blood cell receptor-bearing cells from the bone marrow of multiple myeloma patients suppressed responses of the multiple myeloma patients' PBL's to autologous mitomycin C-treated bone marrow plasma cells and to allogeneic stimuli in one-way mixed leukocyte culture. Complement receptor-bearing cells suppressed the response to pokeweed mitogen. The presence of lymphocytes in the marrow compartment that are capable of suppressing the response of myeloma patients' PBL's to plasma cell antigens may be significant in the pathogenesis of multiple myeloma.

Topics: Bone Marrow; Complement System Proteins; Concanavalin A; Female; Humans; Hypergammaglobulinemia; Immunity; Immunosuppression Therapy; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Multiple Myeloma; Phytohemagglutinins; Pokeweed Mitogens; Rosette Formation; T-Lymphocytes

Persistence of virus and a marked hypergammaglobulinemia are consistent features observed in mink with Aleutian disease virus infection. These events may result from altered lymphocyte function in infected mink. To test this possibility we determined the ability of lymphocytes from infected mink to respond to phytolectins (PHA and Con A), and a specific antigen (KLH) in a lymphocyte transformation test and quantitated the number of lymphocytes bearing surface immunoglobulin. Infected mink had a significantly lower response than normal mink to PHA and Con A (P less than 0.025), and the difference in the responses increased progressively with time post-infection. Infected mink immunized with KLH also had a decreased ability to respond to this antigen when compared to normal immunized mink (P less than 0.001). The number of lymphocytes bearing surface immunoglobulin was significantly elevated in three of 10 mink infected for 10 weeks, and in all of seven mink infected 32 weeks (P less than 0.001).

Topics: Aleutian Mink Disease; Animals; Antibodies, Viral; Antigen-Antibody Reactions; B-Lymphocytes; Concanavalin A; Dose-Response Relationship, Drug; Female; Fluorescent Antibody Technique; Hemocyanins; Hypergammaglobulinemia; Lectins; Lymphocyte Activation; Lymphocytes; Male; Mink; Receptors, Antigen, B-Cell; T-Lymphocytes; Thymidine; Time Factors; Tritium

The peripheral blood lymphocytes of a patient with massive hyperimmunoglobulinaemia E were used for in vitro studies. The serum IgE ranged from 140,000-210,000 u/ml. Peripheral blood lymphocytes had approximately 7% of cells staining for surface IgE. When these cells were cultured in vitro, IgE was produced as measured by the double antibody radioimmunoassay technique. The total IgE produced ranged from 140 to 484 units per 24 hr in different cultures. IgE production was greatest in the first 24 hr of culture and declined progressively thereafter. Some cultures still had measurable IgE at 48 hr. If the lymphocytes staining for surface IgE were the cells producing the IgE, it was estimated that between 1-7 and 2-8 molecules per cell per second were produced. No definite effect of concanavalin A, pokeweed mitogen or phytohaemagglutinin on in vitro IgE production could be demonstrated under the conditions of these experiments.

Topics: Cell Fractionation; Cell Membrane; Cell Survival; Cells, Cultured; Concanavalin A; Eosinophilia; Humans; Hypergammaglobulinemia; Immunoglobulin E; Lectins; Leukocyte Count; Lymphocytes; Receptors, Antigen, B-Cell; Time Factors