Shifts in immunoglobulin (IgG,IgM and IgA) levels in the milk of southern elephant seals,at Potter Peninsula,King George Island,Antarctica

We quantified immunoglobulins (Ig) in mammary secretions of 12 female southern elephant seals ( Mirounga leonina) at King George Island, Antarctica, using single radial immunodiffusion on agarose plates. Seals were chemically immobilized for milk sample collection at four time points during the 3- to 4-week suckling period. All three major mammalian immunoglobulins (IgG, IgM, IgA) were detected in southern-elephant seal milk. Total immunoglobulin levels and the ratio of Ig subclasses varied throughout the suckling period. Total immunoglobulin levels were highest on the 1st day of lactation, when they represented over 57% of the mean total protein concentration of the milk, and declined steadily throughout lactation, representing approximately 40% of the mean total protein concentration at the end of the suckling period. IgG was the most abundant immunoglobulin class (85.93-93.78% of total milk immunoglobulins), followed by IgM (6.06-13.93%), and IgA (0.14-0.23%). There was no significant difference in IgA levels throughout the suckling period. IgG levels were significantly lower during the second stage (3-6 days post-parturition) than during the first, third or fourth stages (1, 13-15, and 19-25 days post-parturition, respectively). IgM levels were highest during the first stage of lactation; these values were significantly higher than levels measured during the second, third and fourth stages of lactation. Transfer of passive immunity from female to offspring in other mammalian species is correlated with the subclass of immunoglobulin secreted in the milk; species acquiring passive immunity in utero, via the placenta, secrete a preponderance of IgA, whereas species acquiring immunity post-partum, via lacteal secretions and gut resorption, secrete a preponderance of IgG. The Ig patterns and concentrations observed in our study of southern elephant seals are consistent with an important role of post-partum transmission of passive immunity during the pinniped lactation period.     

Nephelometry determined serum immunoglobulin isotypes in healthy Thai children aged 2-15 years

Knowledge of what constitute normal serum immunoglobulin (Ig) concentrations are important for the diagnosis of immunologic disorders. Data on normal Ig evaluated by nephelometry are limited in healthy Asian children, none being available for Thai children. One hundred and forty-eight healthy Thai children aged 2-15 years were tested for serum immunoglobulins G, A, M, G1, G2, G3, and G4 (Ig G, A, M, G1, G2, G3, and G4) by nephelometry. Sixty-three percent were girls of median interquartile range age 6.9 (4.8-9.7) years. The geometric means for each Ig were summarized and categorized by age. Statistical analyses were used to compare Igs between sexes and age groups, and to compare IgG in this study with data from other published studies. The average ratios of IgG subclasses/IgG for Ig G1:2:3:4 were 66:22:5:7%. IgG, IgA, IgG2, and IgG3 concentrations showed a gradual increase with increasing age. There were no significant sex differences for any immunoglobulin isotype (P= 0.971). Our mean IgG concentration was lower than that measured by the radial diffusion method in healthy Thai children (P < 0.05). In all age groups, the mean IgG concentration in our study was significantly higher than that reported in Turkish and USA children, evaluated by the nephelometric and radial diffusion techniques, respectively (both P < 0.001). This study provides information about normal Ig concentrations measured by nephelometry in healthy Asian children and illustrates the importance of ascertaining normal Ig values for age- and ethnic-matched controls using the same assay to diagnose immunologic disorders correctly.     

Preferential expression of the systemic lupus erythematosus-associated idiotype 8.12 in sera containing monoclonal immunoglobulins

The 8.12 idiotype defines a population of anti-DNA antibodies present in the serum of patients with systemic lupus erythematosus. As part of our studies to elucidate the genetic origin and structural features of anti-DNA antibodies, we examined monoclonal immunoglobulin (Ig)-containing sera from 706 patients for expression of the 8.12 idiotype. We found 41 such sera to have significant 8.12 reactivity (greater than 4 SD above the mean of normal controls) and demonstrated that in 24 of these sera (8 IgM, 14 IgG, and 2 IgA) this reactivity could be localized to the monoclonal protein. In addition, 12 of the 8.12-reactive monoclonal Ig (11 IgG and 1 IgA) bind dsDNA. In the other 17 sera, the 8.12 reactivity could be attributed to polyclonal antibody. These findings provide further evidence that the serum monoclonal Ig frequently express the antigenic and idiotypic reactivities of autoantibodies. Furthermore, these data support the contention that anti-DNA specificity may result from somatic diversification of germ-line Ig gene sequences.     

Echinococcus multilocularis: Immunoglobulin and antibody response in C57BL6J mice

Each of 50 male C57BL/6J mice was infected intraperitoneally with 50 cysts of Echinococcus multilocularis. At 2, 4, 6, 8, and 14 weeks after infection, 10 mice were sacrificed, their larval cyst masses weighed, and their sera collected. Each serum sample from uninfected control and infected mice was adsorbed twice with two batches of E. multilocularis antigen conjugated to Sepharose beads. The concentrations of IgG1, IgG2a, IgG2b, IgM, and IgA in unadsorbed and IgG1, IgG2b, and IgM in adsorbed sera were quantified by the radial immunodiffusion technique. Hydatid mice produced increasingly large amounts of IgG1 and IgM; small measurable increases of IgG2b and no significant increases of IgG2a and IgA were observed during the course of infection. During the rapid growth phase of the cysts (6 to 14 weeks) IgG1 antibodies were found to range from 86 to 93% and IgM antibodies from 17 to 33% of the total IgG1 and IgM. However, the actual protein concentrations of IgM antibodies (761 and 1215 mg/dl) were higher than the sum of the protein concentrations of IgG1 and IgG2b antibodies (411 and 779 mg/dl). The significance of the relative concentrations of IgM, IgG1, IgG2a, and IgG2b antibodies is discussed with reference to their effectiveness in antibody-dependent cellular cytotoxicity and complement-mediated lysis in the control of alveolar hydatid disease.     

Detection of disease-specific augmentation of abnormal immunoglobulin G in sera of patients with rheumatoid arthritis

Galactose-free immunoglobulin G (IgG), which is known to be higher in the sera of patients with rheumatoid arthritis, was prepared from IgG of healthy volunteers using enzymes. Its reactivity to lectins was analyzed. The galactose-free IgG showed no reactivity to Ricinus communis agglutinin 120 but displayed greater reactivity to concanavalin A and Lens culinaris lectin than did intact human IgG. Then, IgG in serum samples was bound to protein A immobilized on a nitrocellulose membrane, and its reactivity to biotinylated concanavalin A was measured with streptavidin-conjugated horseradish peroxidase. When the reactivity to concanavalin A of IgG in sera from healthy individuals and patients with rheumatoid arthritis (RA), osteoarthritis, systemic lupus erythematosus, or hepatic disease was compared, higher levels were shown in patients with RA, notably in 60% of the seronegative patients and 80% of the early phase patients. Therefore, it was suggested that augmentation of the abnormal IgG in sera was highly specific to patients with RA and that this novel serum test could be very useful for an accurate diagnosis of this disease.     

Immunoglobulin concentration in Atlantic cod, Gadus morhua L., serum and cross-reactivity between anti-cod-antibodies and immunoglobulins from other species

The immunoglobulin (Ig) level in serum from Atlantic cod, Gudus morhua L. (Teleostomi, Gadiformes), was measured using ELISA. Cod serum contains 5.62 ± 0.19 mg Ig ml, which constitute 17.2% of the total serum proteins.
Polyclonal and monoclonal antibodies (Ab) against cod-Ig were used for cross-reactivity studies in sera from other species. The cross-reaction with polyclonal Ab was high in gadifom fish, and low or absent in the other tested species. Immunoprecipitation showed that the Ab only binds to the Ig of the serum from the other species. The results within the gadiform group indicate that (1) Gadidae and Lotidae are more closely related to each other than to Merluccidae, (2) Phycidae is more distant related to Lotidae than earlier considered, (3) Zoarcidae seem to be more distant related to Gadus than other species of Gadiformes. These results support recent revisions of the systematics of Gadiformes.
Monoclonal Ab against the heavy chain of cod-Ig show no, or small (< 15%) cross-reactions with serum from gadiform species. One monoclonal Ab against the light chain shows high cross-reaction and also binds to Ig from species outside the Gadiformes, indicating that the light chain of Ig might be more conserved than the heavy chain.     

Identification of target antigens of self‐reactive IgG in intravenous immunoglobulin preparations

Intravenous immunoglobulin (IVIg) contains a wide range of self‐reactive immunoglobulins (Ig) G. Acidic pH is known to increase the reactivity of purified IgG with self‐antigens. We describe here the target antigens of IgG autoantibodies in IVIg and analyze the influence of acidic pH on IgG reactivities. We used 2‐DE and immunoblotting with protein extracts of human umbilical vein endothelial cells (HUVEC) and HEp‐2 cells. Two IVIg preparations obtained by ethanol fractionation [one with an acidic pH step (acidic‐IVIg) and one with β‐propiolactone (propiolactone‐IVIg)] and a pool of sera from 12 healthy individuals were tested. Serum IgG of 3 healthy individuals and IgG purified from the same sera with elution at pH 2.8 were also tested individually. Finally, propiolactone‐IVIg was acidified at pH 2.8. IgG obtained with a step at low pH recognized many more target spots than IgG obtained without acidic pH. Our findings demonstrate that an acidic pH step artificially enlarges the repertoire of self‐reactive IgG. Thus, protein spots recognized by IgG in propiolactone‐IVIg represent the core set of self‐antigens targeted by IVIg. Overall, 96 proteins were identified by MS. Fourteen were recognized in both extracts including glycolysis proteins such as α‐enolase, RNA processing and cytoskeletal proteins such as lamin‐A/C.     

Immunomodulatory effects of ovine serum immunoglobulin in the growing rat

This study aimed to determine whether orally administered ovine serum immunoglobulin (Ig) modulates aspects of immunity such as phagocytosis, lymphocyte proliferation, cytokine production, intestinal and plasma Ig concentrations in growing rats. Forty-five male Sprague-Dawley rats (n = 15/group) were used in the 21-day study, and fed a basal control diet (BD; no Ig) or two test diets: freeze-dried ovine Ig (FDOI) and inactivated ovine Ig (IOI). Phagocytic activity of peripheral blood leukocytes and lymphocyte proliferation in the presence of the mitogen concanavalin A (ConA) was greater (P < 0.05) for the FDOI-fed rats than for the BD- and IOI-fed groups. ConA-stimulated and unstimulated spleen cell culture produced higher (P < 0.05) interferon-γ and interleukin-4, respectively, from rats fed the FDOI than rats fed the BD diet. In the jejunum, ileum and plasma, rats fed FDOI produced higher (P < 0.05) concentrations of secretory IgA (sIgA) than rats fed IOI or BD. Rats fed the FDOI diet had greater jejunal (P = 0.037) and lower plasma (P = 0.025) rat IgG concentrations than rats fed either BD or IOI. In conclusion, an ovine Ig fraction selectively modulated various indices of immune function.     

Echinostoma caproni: kinetics of IgM, IgA and IgG subclasses in the serum and intestine of experimentally infected rats and mice

The kinetics of specific immunoglobulin M, A and IgG subclasses against Echinostoma caproni (Trematoda: Echinostomatidae) were analyzed in serum and intestinal fluid of two host species (Wistar rats and ICR mice) in which the course of the infection markedly differs. In rats, the worms were rapidly expelled, whereas E. caproni evokes in mice long-lasting infection. The pattern of antibody responses in both serum and intestinal samples was different in each host species. Serum responses in mice were characterized by significant increases of IgM, IgA, total IgG, IgG1 and IgG3, but not IgG2a. In contrast, serum responses in rats showed elevated levels of IgM, probably in relation to thymus-independent antigens, and slight increases of total IgG, IgG1 and IgG2a. At the intestinal level, increases of IgM and IgA levels were observed in mice. In regard to IgG subclasses, increases in both IgG1 and IgG2a were detected. Later decreases to normal values in IgG2a were also detected. In rats, only increases in total IgG and IgG2a were found. According to our results the development of long-lasting E. caproni infections in mice appears to be associated with a dominance of Th2 responses at the systemic level and balanced Th1/Th2 responses at the local level, characterized by initial increases in IgG1 and IgG2a levels. In contrast, the worm expulsion appears to be related to increases in local IgG2a levels.     

Enterobacterial 38-kDa outer membrane protein is an age-dependent molecular marker of innate immunity and immunoglobulin deficiency as results from its reactivity with IgG and IgA antibody

In earlier studies on an animal model we observed protective properties of outer membrane proteins (OMPs) of Shigella, Hafnia, and Escherichia coli strains. In order to investigate human sera for reactivity with OMPs we subjected these proteins to immunoblotting with umbilical cord plasma and sera from children and adults. The IgG and IgA antibodies interacted primarily with a 38-kDa protein, in similar way for several enterobacterial strains, but different for Pseudomonas aeruginosa. This observation prompted us to determine the reactivity with the purified 38-kDa OMP in the sera of several groups of children. The reactivity of the protein from Shigella flexneri serotype 3a with sera in ELISA was age dependent, increasing from low reactivity in infants to the adult antibody level. The IgG and IgA antibody specific response thus revealed the normal pattern of immunity. The level of IgA and IgG antibody was significantly low in child patients with IgA and/or IgG immunoglobulin deficiencies, but was at the healthy control level in children with recurrent respiratory tract inflammation. These data correlated with total IgA and IgG levels in immunoglobulin-deficient children. The results indicate that this protein may serve as an immunodiagnostic marker, but also as an antigen carrier in vaccines.     

Generation of low m.w., C3-bearing immunoglobulin in human serum

The generation of low m.w. C3-bearing immunoglobulin (lg) in normal human serum by an immune complex (IC) model was investigated in vitro by using discontinuous sucrose density gradient centrifugation (DGC) and an assay that measures C3-bearing Ig. In this method developed to measure circulating IC, all C3 and C3-bearing material is precipitated from serum by using anti-C3 sera in C3d antibody excess, and immune precipitated, C3-bearing Ig is quantitated by the uptake of 125I-5S-anti-IgG. When plasma from patients with clinically active systemic lupus erythematosus was assayed after DGC, most of the reactive material was low m.w. (7S), rather than greater than or equal to 19S as expected for IC, in agreement with a previous report. Low m.w., C3-bearing Ig was found in normal EDTA plasma after extended storage at -29 degrees C but not after storage at -70 degrees C. Such material was also generated in normal human serum during incubation at 37 degrees C and its generation was stimulated by the addition of an IC model, high m.w., heat-aggregated IgG (HMW-HAIgG). In experiments in which the participation of serum IgG was monitored by the addition of 125I-7S-IgG and 131I-HMW-HAIgG was used as an IC model, low m.w., C3-bearing Ig was generated exclusively from serum IgG and the amount generated was proportional to the concentration of 131I-HMW-HAIgG. No significant decrease in sedimentation of 131I-HMW-HAIgG was observed, but the ability of anti-C3 sera to precipitate 131I-HMW-HAIgG decreased 66% 4 hr after initial C activation. These results indicate that generation of nascent C3b in serum results in its interaction with monomeric serum IgG, producing low m.w., C3-bearing IgG. In addition, the data indicate that circulating IC that activate C have a brief time span during which they can be detected by methods that depend upon the binding of C3.     

Yolk-sac transmission and post-hatching ontogeny of serum immunoglobulins in the duck (Anas platyrhynchos)

1. To investigate the immunoglobulin (Ig) class which is active in yolk-sac transmission of maternal antibodies in ducks, sera from laying ducks, yolks from their eggs, and sera from ducklings 0-87 days of age were examined by immunoelectrophoresis (IE), and Na2SO4-precipitated Igs from these sera and yolks were run in polyacrylamide gel electrophoresis (PAGE) under reducing conditions. 2. In yolk, 7.8S IgG was greatly enriched compared to 5.7S IgG and IgM, and was the only Ig to reach the sera of newly hatched ducklings. 3. The levels of maternally derived 7.8S IgG in duckling sera decreased after 5 days of age, reaching minimum levels at about 14 days of age. 4. Increases in the serum levels of 7.8S IgG, 5.7S IgG and IgM occurred after 20 days of age, reflecting de novo synthesis by the duckling, and the adult serum profile was achieved by 71 days of age. 5. The involvement of 7.8S rather than 5.7S IgG in yolk-sac transmission was probably determined by the additional heavy chain components of this molecule.     

Serum antibodies to group A streptococcal extracellular and cell-associated antigens in Egyptians with post-streptococcal diseases

We investigated serum antibodies to a comprehensive array of group A streptococcal antigens and superantigens in Egyptian subjects. Antibodies to Streptococcus pyogenes cell-associated proteins and to proteins released by rapidly dividing S. pyogenes were compared in four patient groups with different post-streptococcal diseases and in healthy controls. Enzyme-linked immunosorbent assays showed that total Ig and IgG to extracellular antigens were significantly higher in patients with acute rheumatic fever (ARF) compared to healthy controls, but no differences were found in either total Ig or IgG titres to cell-associated proteins between any of the groups. Western blotting showed that multiple extracellular and cell-associated antigens, covering a wide range of molecular masses, were recognised by all sera, including healthy controls. No evidence was obtained for putative dominant antigens associated with any disease group, although a low molecular mass cell-associated protein (approximately 4 kDa) was clearly recognised by two-thirds of subjects irrespective of disease status. These findings demonstrate that raised serum Ig and IgG titres to extracellular, but not cell-associated, S. pyogenes antigens are a feature of ARF in this population, and suggest that multiple S. pyogenes antigens contribute to this response.     

The effects of cobalt and iodine supplementation of the pregnant ewe diet on immunoglobulin G, vitamin E, T3 and T4 levels in the progeny

Sixty twin-bearing ewes were allocated to one of four dietary treatments investigating the effects of supplementary iodine or cobalt during late pregnancy on lamb serum immunoglobulin G (IgG), triiodothyronine (T3), thyroxine (T4) and vitamin E concentrations, and lamb IgG absorption efficiency. Ewes were offered grass silage ad libitum supplemented with 800 g per ewe per day of a 190 g/kg crude protein (CP) concentrate from day 126 of gestation until parturition plus one of the following supplements (n = 15 per treatment); no supplement (C); 26.6 mg iodine per day for final 3 weeks pre partum (I-3); 26.6 mg iodine/day for final week pre partum (I-1); 20 mg cobalt/day for final 3 weeks pre partum (Co-3). Lambs were blood sampled at 24 and 72 h post partum for serum IgG and vitamin E concentrations. Ten lambs from C and I-3 were blood sampled at 1 h post partum for serum IgG, vitamin E, T3 and T4 concentrations. There were no differences in serum IgG, vitamin E or T4 values (P > 0.05) at 1 h post partum between lambs born to the C and I-3 ewes. T3 levels were lower in I-3 compared with C progeny (P < 0.05). Supplemental iodine reduced colostral IgG absorption efficiency (P < 0.001) and lamb serum IgG concentrations at 24 and 72 h post partum (P < 0.001). Serum vitamin E concentration in I-3 and I-1 lambs was lower than in Co-3 lambs at 24 h post partum, while at 72 h post partum I-3, I-1 and Co-3 lambs had significantly lower concentrations than C lambs (P < 0.001). Supplementing the ewe's diet with 26.6 mg/day of iodine for the final week of pregnancy reduced lamb serum IgG concentration at 24 and 72 h post partum. The lower total and free T3 values in the progeny of I-3-treated ewes suggest interference in the synthesis and metabolism of thyroid hormones when ewes receive excessive dietary iodine for 3 weeks immediately pre partum. Based on these findings, the indications are that the toxicity level for iodine in the diet of the pregnant ewe should be lowered to 20 mg per ewe per day, equivalent to 40% of its current level. The finding that high-level cobalt supplementation during the final 3 weeks of pregnancy will have a negative effect on serum vitamin E concentration at 72 h post partum is a new and significant finding and previously has not been reported in the literature.     

Human antibodies to phosphocholine. IgG anti-PC antibodies express restricted numbers of V and C regions

We examined the IgG subclass composition and isoelectric focusing (IEF) spectrotype pattern of naturally occurring human IgG antibodies that bind phosphocholine (PC) and found direct evidence for restricted expression of both V and C regions among these antibodies. In most individuals, the isotype of these IgG anti-PC antibodies was primarily IgG2. However, serum from some individuals contained significant amounts of IgG1 and IgG3 anti-PC antibodies. We also found that in individual sera, anti-PC antibodies are pauciclonal, as demonstrated by restricted spectrotypic patterns of the anti-PC antibodies. The IEF pattern of these antibodies were for the most part unique for each individual. In some sera, certain anti-PC antibodies with isoelectric points of basic pH bound PC conjugated to bovine serum albumin (PC-BSA) but did not bind pneumococcal C-carbohydrate bearing PC determinants. In two individuals, we found that the spectrotypes that bound only PC-BSA were of the IgG1 subclass. Taken together, these findings demonstrate that within individual sera, human antibodies to PC are quite restricted in both V and C region expression, and furthermore, these V and C regions of human Ig may not randomly associate.     

Immunoglobulin responses of northern elephant and Pacific harbor seals naturally infected with Otostrongylus circumlitus

Immunoglobulin (Ig) binding patterns of Pacific harbor seals (PHS, Phoca vitulina richardsi) and northern elephant seals (NES, Mirounga angustirostris) to tissues of adult Otostrongylus circumlitus were examined by immunoblotting to investigate the role of age in the unusual response of juvenile NES to infection with O. circumlitus. Serum was taken from NES between March 1997 and March 2001 and from PHS between May 1996 and August 1999. The serum of seals infected with O. circumlitus contained antibodies that bound to all nematode tissues examined. Intensity of band staining on Western blots suggested that there were higher levels of antibody recognizing the excretory-secretory (ES) glands in the serum of NES that were 1 yr and older and in the majority of PHS compared with that in 2- to 9-mo-old NES. All juvenile NES infected with O. circumlitus and a proportion of the PHS and older NES infected with O. circumlitus contained Ig specific to a 28 kDa protein band that was dominant in the female reproductive tract of the nematode. The Ig binding patterns of NES and PHS to adult Parafilaroides sp., larval Pseudoterranova sp., and larval and adult Anisakis sp. differed sufficiently from that of O. circumlitus that immunoblotting for the 28 kDa protein could be useful for diagnosis of this parasite in juvenile NES. The banding patterns suggest that O. circumlitus nematodes die and disintegrate in PHS and NES and that NES of 1 yr and older and most PHS respond differently to the ES glands than 2- to 9-mo-old NES.     

Prevalence of antibodies to specific infectious agents in bovine fetuses from a slaughterhouse in Minnesota

Sera from 486 bovine fetuses, approximately 60 to 270 days of gestation, were collected at slaughter and tested for the presence of immunoglobulins (Ig). One hundred ten (27%) of the sera were positive for IgG and/or IgM. The earliest age at which fetuses tested positive for IgM and IgG was estimated to be 100 and 120 days, respectively. Ig concentration increased with increased age of the fetus. Sera that were positive for Ig were tested for the presence of specific antibodies to five different infectious agents. Bovine parvovirus antibodies were found in 99 of 110 sera (90%) by hemagglutination inhibition (HI) test. However, only 35 (31.8%) of these sera were positive by serum neutralization (SN) test. Antibodies to parainfluenza-3 virus were detected in 30 sera (27%) by HI test and in 20 sera (18%) by SN test. Five (4%) sera contained SN antibodies to bovine viral diarrhea virus. Only one (0.9%) serum sample contained SN antibodies to infectious bovine rhinotracheitis virus. None of the sera had antibodies against five Leptospira spp. Results of this study suggest that bovine parvovirus may be a potential cause of reproductive problems in cattle.     

Long-term study of serum glycosyl-transferase levels in pregnant women and their newborn infants

1. The authors have studied changes of glucosyl-, galactosyl- and sialyl-transferase activities in the sera of women during pregnancy and the early post-partum period, and in neonates from birth to 1 yr of age. 2. Galactosyl- and glucosyl-transferase activities throughout pregnancy were high in comparison to control values, and increased with advancing gestation. In the early post-partum period, the activities of these enzymes decreased markedly, reaching values similar to those of control subjects. 3. There were no variations, however, in serum sialyl-transferase activity at any stage of pregnancy or the post-partum period. In newborn infants, serum glucosyl- and sialyl-transferase activities were identical to control values. 4. Galactosyl-transferase activity was high at birth, decreased progressively and returned to the normal range only after 1 yr. 5. The physiological significance of these glycosyl-transferases in the sera of pregnant women and newborn infants is discussed.     

Evidence for shared idiotypy expressed by the IgM, IgG, and IgA serum proteins of a patient with a complex multiple paraprotein disorder.

The results of a comparative idiotypic analysis of multiple Ig paraproteins isolated from the serum of an individual patient, Ca, with Sj?gren's syndrome and Waldenstr?m's macroglobulinemia are reported. At initial presentation, Ca serum was found to contain two major paraproteins, an IgMkappa and an IgGkappa, together with a small elevation in the level of IgA protein. The patient's clinical course was characterized by dramatic and opposing changes in the respective serum levels of the IgMkappa and IgGkappa paraproteins over an extended time period that coincided in part with received chemotherapy. Idiotypic antigenic analysis of the IgMkappa and IgGkappa paraproteins revealed that the two monotypic proteins shared identical idiotypic determinants. The Ca IgA serum fraction, specifically isolated by an immunoabsorbent and free of any IgG and IgM, was shown to possess idiotypic determinants identical to the IgG and IgM proteins. In extensive tests of specificity, the idiotypic determinants shared by Ca IgM, IgG, and IgA proteins were not present in large excesses of heterologous IgM and IgG, nor on Ig molecules contained in a large number of normal and myeloma sera.     

Human hybrid immunoglobulin M containing immunoglobulin A

Summary Some hybridoma clones made by fusion of a human lymphoblastoid cell line, HO323 with human B lymphocytes, secreted not only IgA but also IgM-like immunoglobulin molecules. The IgM-like immunoglobulin had a molecular size of 900 K which corresponded to that of IgM. Immunochemical analyses revealed that the IgM-like immunoglobulin contained two monomeric IgA and three monomeric IgM molecules. In the IgA moieties, half of original light chains were replaced withx chains derived from the IgM, and vice versa.