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Peripheral blood cells from patients with myelodysplastic syndromes were assayed for B-cell and immunoregulatory T-cell functions. The B/T cell ratio in myelodysplastic patients (n = 11) was significantly higher than in controls (n = 12). These patients had a reduction in total T-cell (OKT3+) frequency and in T-cell subset (OKT4+/OKT8+) ratios. The response of patients' cells to both pokeweed mitogen (PWM) and phytohemagglutinin (PHA) was reduced, but patients' B cells responded normally to stimulation with Staphylococcus aureus Cowan (SAC). The levels of IgG and IgM detected in 7-day culture supernatants of PWM-stimulated patient and control cells were similar. Normal B-cell and immunoregulatory T-cell functions were subsequently demonstrated in allogeneic co-culture combinations of enriched T and B cells from patients and controls. The data presented indicate that the frequent infections of myelodysplastic patients are not causally related to impaired humoral mechanisms. The data also favor the possibility that the stem cell disorder in these syndromes is functionally expressed at a subsequent stage to the lymphoid differentiation pathway.

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Peripheral blood samples collected from normal individuals and patients with benign monoclonal gammopathy and multiple myeloma were separated and assayed for their T- and B-cell subpopulations as well as immunoglobulin (IgG, IgM) synthesis in vitro. To rule out any functional or quantitative alterations related to therapy, only newly diagnosed multiple myeloma patients and subjects with benign monoclonal gammopathy were included in our study. Multiple myeloma patients were further subdivided into two groups. Group A consisted of patients with low and intermediate tumor burdens, while group B included patients with high tumor mass. B- and T-cell subset analysis revealed an abnormal ratio between B/T and OKT4+/OKT8+ lymphocytes compared to healthy controls. These alterations were especially prominent in group B multiple myeloma. Immunoglobulin synthesis was studied in pokeweed-mitogen-stimulated lymphocyte cultures. The results indicate that the failure to synthesize and secrete immunoglobulin resides within the B-cell lineage and is probably due to a functional B-cell defect. T-cell immunoregulatory functions seem to be unaffected in both multiple myleoma and benign monoclonal gammopathy patients.

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Immunoglobulin-lipid complexes (SILC) are found in the serum of all patients with monoclonal gammopathy. Fractionation by density gradient ultracentrifugation, Sephadex G-200 chromatography and Sepharose protein A affinity, followed by extensive immunoassaying for immunoglobulins and lipoproteins, does not confirm the accepted assumption that SILC are immune complexes between monoclonal immunoglobulins and lipoproteins. Lipid extraction of monoclonal fractions isolated on protein A columns followed by thin-layer chromatography shows a lipid pattern characteristic of the one found in cellular membranes. It is proposed that SILC are hydrophobic complexes between immunoglobulins and lipids, as described in membranes of B lymphocytes.

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Peripheral blood samples from normal individuals and from patients with benign monoclonal gammopathy or multiple myeloma were separated and assayed by immunofluorescence and rosette formation for T, B, TG and TM subpopulations. When compared with normal individuals and multiple myeloma patients, the benign monoclonal gammopathy patients could be divided into 2 groups. The 1st group demonstrated a T/B ratio similar to normal individuals, whereas in the 2nd group the ratio resembled that of the myeloma patients, with a decrease in the fraction of T lymphocytes, accompanied by an increased number of B lymphocytes. An analysis of the monoclonal Ig fraction levels indicated that the 2 groups differ in this respect as well. In the 1st group, the level of the monoclonal immunoglobulin was stable, with small fluctuations. The 2nd group demonstrated a general increasing M-component, especially in the 4-6 months preceding the study. The 2 benign monoclonal gammopathy groups exhibited a trend to a lower TM/TG ratio compared to normals; this change is more prominent in the 2nd group. Analysis of the T lymphocyte subpopulations indicated an overall decrease in the fraction of TM multiple myeloma. The above-mentioned parameters might thus aid in discriminating among BMG patients with regard to their tendency towards a malignant transformation.

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Immunoelectrophoresis and immunodiffusion of some IgD myeloma proteins fail to demonstrate precipitin bands between the light chain and anti-light chain serum. Reduction and alkylation of purified IgD preparation was found to render the molecule reactive to anti-lambda serum. Iodinated IgD myeloma protein was successfully precipitated by both anti-delta and anti-lambda antibodies. Both antisera precipitated heavy and light chains of a MW of 70,000 and 24,000 daltons respectively. In addition, a band of 39,000 daltons was also evident. Reduction and alkylation of the iodinated molecule, followed by precipitation with anti-delta serum demonstrated only the 70,000 and 39,000 daltons bands. The present report indicates that by sensitive techniques, such as iodination and immunoprecipitation, non-reactive hidden light chains can be detected in IgD lambda molecules.

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An asymptomatic hypercalcemic IgG-Kappa myeloma patient is presented. A calcium-IgG complex was isolated and purified from the serum by column chromatography. Following further purification on a Sepharose protein A column, the IgG-Kappa molecule did not contain any detectable amount of calcium, indicating that calcium is loosely bound to IgG. The monoclonal IgG demonstrated a strong calcium binding capacity in vitro. The calcium-IgG complex in the serum was shown not to be saturated and thus could absorb more ionized calcium. In view of the presence of an abnormal monoclonal IgG capable of binding excess calcium, and the fact that the asymptomatic patient did not respond to the antihypercalcemic drugs, the treatment was stopped.

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Hybrids derived from the fusion of cell lines representing different maturation stages were studied for their membrane and cellular immunoglobulin expression. The hybrids can be subdivided into 3 groups, with one common parental line in each group. In the first group, Raji cells represent the common parent: it contains small amounts of membrane and cytoplasmic mu (mu) and kappa (kappa) chains. In the second group, PUT is the common parent, an ouabain and TG-resistant subline of the BL-derived P3HR-1 line. PUT contains a truncated intracellular mu chain. The third group consists of hybrids between K562, an EBV-negative human erythroleukemia line and 2 different BL lines. Membrane-immunoglobulin expression was intermediate between the parental lines in the first two groups derived from the fusion of 2 BL lines. In the third group, hybridization with the K562 cell suppressed the membrane-Ig expression of the B-cell partner. Total cellular immunoglobulin determinations showed that some cells synthesized light chains in excess of heavy chains, others contained an excess of heavy chains, while still others had equal amounts of heavy and light chains. The hybrids showed a variety of patterns, including amplification of the parental phenotypes, appearance of new phenotypic combinations, and eclipse of one or both parental phenotypes. A comparison of the total and the membrane-associated immunoglobulin patterns suggests independent handling of intracellular and membrane immunoglobulin synthesis.

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A calcium binding IgG was isolated and purified by column chromatography from serum of a myeloma patient with asymptomatic hypercalcaemia. The myeloma IgG, characterized as an IgG kappa, revealed a normal sized heavy chain (56 000 dalton), and a light chain of 31 000 dalton. Another population of IgG separated and purified from the same patient's serum did not bind calcium and had a normal 26 000 dalton light chain. Calcium binding activity in vitro is optimal at pH 8.0, and reaches its maximum after 3 h of 45Ca myeloma IgG incubation. Cleavage of the purified IgG by trypsin yielded peptides which were further isolated by column chromatography and characterized as Fab and Fc fragments. Light and heavy chains were obtained by reacting the immunoglobulin with dithiothreitol and iodoacetamide followed by Sephadex G-100 chromatography. Calcium binding activity was proved to be associated with Fab IgG fragment. Preparates containing Fc, heavy or light chains did not bind calcium in vitro.

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Absolute concentrations of IgA in nasal secretions and concentrations of immunoglobulins in serum were determined in a prospective study of acute respiratory tract infections. The study was carried out in 48 children aged six months to four years liveing in a kibbutz with a homogeneous environment. No correlation was demonstrated between mean base-line levels of secretory IgA or serum IgA and number of episodes of acute resporatory tract infection. However, children who responded to infection by the production of higher levels of secretory IgA had a lower incidence of acute respiratory tract infection than those who did not. Thisfinding supports the hypothesis that the responsiveness of the host in the production of secretory IgA during infection is important in protection against mucosal infections.

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When Newcastle disease virus (NDV) is treated with NP-40 and ether a membrane fraction of 150,000 m.w. is obtained. This fraction which is composed of two polypeptides with m.w. of 56,000 and 76,000 was used in a radioimmunoassay (RIA). The assay was developed for both antigen and antibody and was found to be reproducible, specific, and highly sensitive. Titers of 1:51,200 were determined by RIA as compared to 1:4 by agar gel diffusion and 1:200 by hemaglutination inhibition (HI). As little as 5 ng of viral protein were detected by RIA inhibition technique. Labeled antigen could be stored in the presence of serum, KCI and Triton X-100 at -20 degrees C for as long as 6 weeks and retained similar reactivity as fresh reagent.

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