Vincent Yakulis

Changes in Lymphocyte Surface Immunoglobulins in Myeloma and the Effect of an RNA-Containing Plasma Factor

Patients with multiple myeloma have a reduced number of B lymphocytes with normal surface immunoglobulin. When, however, anti-idiotypic antiserums to the respective myeloma globulins were used for the visualization of surface immunoglobulin by indirect immunofluorescence, a large number of surface immunoglobulin carrying lymphocytes were detected. The possibility of absorption of these monoclonal surface immunoglobulins from the surrounding plasma was excluded by showing their resynthesis after removal from the cells by trypsinization. The change in the character of surface immunoglobulin was reproduced on normal lymphocytes with an RNA-rich extract from the plasma of patients with myeloma; this effect was inhibited by RNase and cycloheximide. These findings suggest the possibility that an RNA-containing plasma factor transmits information for synthesis of surface immunoglobulins between myeloma cells and normal lymphocytes. This mechanism may contribute to the dysfunction of B lymphocytes in patients with myeloma, leading to immunologic deficiency.

Severe Hypersensitivity to Diphenylhydantoin with Circulating Antibodies to the Drug

Excerpt An infrequent adverse reaction to diphenylhydantoin (DPH) is a mononucleosis-like syndrome (1, 2). We report here on such a patient, in whom polyclonal IgG antibodies to DPH were detected. ...

Two myeloma globulins (IgG and IgA) in one subject and one cell line.

Abstract This paper describes the clinical history of a patient who produced two distinct myeloma globulins (IgG and IgA). Immunofluorescent studies revealed the presence of the two myeloma globulins in single plasma cells.

Double myeloma: Production of both IgG type lambda and IgA type lambda myeloma proteins by a single plasma cell line

Abstract Monoclonal immunoglobulins G (IgG) and A (IgA) of the lambda light chain type were present in the serum of a patient with multiple myeloma. Three populations of myeloma cells were seen by immunofluorescence of bone marrow; those containing either IgG or IgA and those staining for both IgG and IgA. Idiotypic determinants present on the variable regions of the two myeloma proteins were immunologically identical and all the myeloma cells contained the same idiotypic determinant. The idiotypic specificity was related more closely to the variable region of the heavy chain than to the light chain. Structural and electrophoretic analysis confirmed that the light chains of the two myeloma proteins were identical. The myeloma in this patient appears to have arisen from a single clone of cells that was capable of synthesizing the constant portions of both the IgG and IgA heavy chain but only a single light and heavy chain variable region. These findings suggest that current concepts of antibody synthesis involving the sequential production of immunoglobulin M (IgM) and IgG antibodies may apply to certain cell lines synthesizing IgG and IgA antibodies as well.

Light-Chain Heterogeneity of Cold Agglutinins

Cold agglutinins with specificity to I or to i antigens of humanadult or cord-blood erythrocytes produced during the course of Mycoplasma pneumoniae infection and infectious mononucleosis contain light chains of K and L types. However, cold agglutinin isolated from the serums of patients with chronic cold-agglutinin hemolytic anemia contains only type K light chains. The experimental evidence suggests that some cold agglutinins contain both types of light chains in the same molecule.

THE DISTRIBUTION OF HEMOGLOBIN A1

Genetic and biochemical considerations, namely the low concentration of hemoglobin A2 in cord blood hemolysates, its absence in the homozygote individual with persistent fetal hemoglobin’ and the primary structure of hemoglobin Lepore’ have produced the generally accepted hypothesis of close linkage of the genes for the delta and beta polypeptide chains. Although there is indirect ~ u p p o r t ~ ’ ~ for the assumption that hemoglobin A2 is present in all cells containing hemoglobin A, direct proof of this distribution pattern of H b A2 has still been missing from the total evidence. It is also not definitely known whether the high F cells of patients with 0-thalassemia minor and of normal infants also contain H b A2, Matioli’s‘ admirable attempts of microelectrophoresis of single red cells of normal adults suggest that this minor fraction might not be present in each cell, but the technique is so formidably difficult that the results are questionable. Distribution patterns on blood films have been studied for hemoglobin F,6 hemoglobin S,7 hemoglobin H8 and hemoglobin M.9’’0 The techniques for such studies are based on abnormal solubility characteristics of these hemoglobins under varying conditions. To our knowledge, no such differences exist between hemoglobin A and Az. However, the immunologic specificity of the &chain, which has been amply confirmed since our original report, can be utilized for the production of immunofluorescent sera which react only with hemoglobin A2 and permit its visualization in single cells. The same is, of course, true of hemoglobin F which is highly antigenic in rabbits. 11

CYTOLOGICAL DETECTION OF PARATHYROID HORMONE BY IMMUNOFLUORESCENCE.

Summary The fluorescent antibody tech™ nic has been utilized to detect and to localize parathyroid hormone in the chief cells of bovine, human and rat parathyroid tissue. Im-munochemical cross-reaction has been found among these species. The oxyphil cells of human parathyroid tissue did not reveal specific fluorescence. This observation is regarded as further evidence that the oxyphil cells do not normally synthesize or store parathyroid hormone. The authors are indebted to Mr. Clarence Sidwell and Mr. Lemuel Hall of the Research Laboratory for technical assistance; to Mrs. Patricia Boulware and Dr. K. Using Wu of the Pathology Service for assistance in tissue preparation and for histologic consultation; and to the Medical Illustration Service for preparing the photographs.

Antigenicity of connective tissue extracts.

Summary 1. Antibodies to rabbit connective tissue have been induced in the guinea pig. 2. Connective tissue extracts from aged rabbits had greater antigenicity than from young animals. 3. Anticonnective tissue serum crossreacted with the cytoplasmic fraction of rabbit leukocytes. 4. Chemical characteristics of the antigenic component of connective tissue remain incompletely explored.

Vitamin B12 binding capacity of serum in B12 deficiency.

Summary 1. Human serum has been found to have a limited binding capacity for Vit. B12. The B12 binding protein, a seromucoid fraction, appears to be normally only approximately 30-40% saturated. In Vit. B12 deficiency the unsaturated binding capacity is normal but total binding capacity is diminished. 2. It is postulated that; the slower than normal disappearance of Co57-B12 from the plasma of B12 deficient individuals is caused by diminished binding capacity in the tissues. The authors wish to express their appreciation to Medical Illustration Service, VA West Side Hospital and to Mr. Lemuel Hall for technical assistance.

Passive Immunity to Murine Plasmacytoma by Rabbit Antiidiotypic Antibody to Myeloma Protein

Summary Antiidiotypic antisera to LPC-1 and MOPC-300 plasmacytoma globulins were produced in rabbits by immunization with the corresponding antigen and exhaustive immunoabsorption with normal BALB/c plasma and other myeloma globulins. IgG fractions of these antisera when given intraperitoneally on three consecutive days after tumor implantation, protected the animal specifically from the grafting of the corresponding plasmacytoma or induced regression of the tumors after their initial grafting and growth. In vitro cytotoxicity of the antisera to plasmacytoma cells was not demonstrated. Plasma of the antisera-treated normal BALB/c mice, though containing antiidiotypic antibody in high titers (320-640), was not cytotoxic to tumor cells. The inhibitory effect on tumor growth can be considered the result of passive immunization against plasmacytoma with xenogeneic humoral antibody.