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Changes in immunoglobulin isotypes and immunoglobulin G (IgG) subclasses during highly active antiretroviral therapy: anti-p24 IgG1 closely parallels the biphasic decline in plasma viremia.

SUMMARY: The effects of highly active antiretroviral therapy (HAART) on immunoglobulin isotypes and immunoglobulin G (IgG) subclasses were studied in 12 patients in early stages of HIV-1 infection. Blood samples were obtained at enrollment and 2, 4, 8, 12, 24, 48, and 120 weeks after initiation of HAART. Immunoglobulin concentrations were determined by nephelometry, and anti-p24-specific IgG and IgG1 levels were determined by an enzyme immunoassay. Overall time changes were analyzed in analysis of variance models. IgG and IgG1 levels showed a marked overall decline, whereas other immunoglobulin isotypes and IgG subclasses did not change significantly. Anti-p24-specific IgG1 levels decreased considerably and significantly more in virus isolation-negative patients than in virus isolation-positive patients, as defined according to the ability to isolate HIV-1 from their CD4+ T cells after initiation of therapy. Anti-p24 IgG levels showed a similar but overall weaker decline in the two groups. However, the anti-p24 IgG1 level followed the biphasic decline in plasma viremia more closely than the anti-p24 IgG level, with an initial sharp decline that leveled off with time. These findings suggest that the main reduction in immunoglobulin levels is caused by reduced HIV-1-specific antigen stimulation rather than a general reduction in immune activation. Using anti-p24 IgG1 as a parameter of response to the effect of HAART merits further investigation.

Adult↗

Monoclonal and polyclonal antibodies to chicken immunoglobulin isotypes specifically detect turkey immunoglobulin isotypes.

Turkey immunoglobulin (Ig) isotypes IgG and IgM were isolated from blood and IgA was isolated from bile. Isolation was accomplished by gel filtration of the ammonium sulphate cut on Sephacryl S-200. Using immunoelectrophoresis and indirect ELISA, the cross-reactivity between antibodies, of monoclonal and polyclonal origin, specific for the Ig isotypes of chicken, and the purified turkey Ig isotypes was evaluated. Commercially available polyclonal antibodies, anti-chicken/IgA (alpha-chain specific, affinity purified), anti-chicken/IgG (Fc-fragment specific) and anti-chicken/IgM (mu-chain specific) showed an interspecies cross-reactivity with the corresponding turkey Ig isotypes. The monoclonal antibody (MAb) AV-G3 specifically detected turkey IgG, whereas MAb M1 reacted exclusively with turkey IgM. This panel of anti-immunoglobulins represents a useful tool for examining the humoral immune responses of turkeys.

Animals↗

Combinations of interleukins 2, 4 and 5 regulate the secretion of murine immunoglobulin isotypes.

Immunoglobulin (Ig) production by lipopolysaccharide (LPS)-stimulated cells in the presence of various combinations of interleukin (IL)2, IL4 and IL5 was examined. IgG1, IgM and IgE secretion was studied using a 3T3-fibroblast filler cell-supported B cell culture system, either at low cell density to support maximal Ig secretion, or at limiting dilution to determine isotype-specific precursor frequencies. In the presence of optimal concentrations of IL5 (2%) and IL2 (3 U/ml), the addition of 1 U/ml of IL4 resulted in the production of 4 ng of IgG1 per input B cell. In contrast, 1000 U/ml of IL4 alone was required to produce equivalent levels of IgG1. IL5 and IL2 increased both the precursor frequency and the amount of IgG1 secreted per clone in the presence of low levels of IL4. On the other hand, IgM secretion was decreased 10-fold by the addition of 10 U/ml IL4 or greater. This was not seen when IL5 was present. The IgM-secreting precursor frequency was unaffected by any of the lymphokines, either singly or in combination. The inhibition of IgM production and subsequent relief of this with IL5 was shown to affect the amount of IgM secreted per clone. IgE secretion was shown to be highly IL4 dependent with only minor reduction in the required concentration following addition of IL5 and IL2. At the clonal level, the majority of IgE-secreting clones (93%) at high IL4 concentrations (200 U/ml) arose from precursors which were able to produce IgM and IgG1. Furthermore, only 3% of the clones secreted IgG1 alone, with a further 3% secreting IgE alone. These results suggest that B cells in vivo are predominantly uncommitted in terms of isotype to be produced, the choice of isotype secreted being dependent on the nature of the stimulus. Overall, this work shows that the isotype secreted by B cells can be regulated using combinations of IL2, IL4 and IL5, and that major effects can be achieved by very small quantities of lymphokines acting in synergy.

Animals↗

In vitro immunoglobulin isotype suppression in immunoglobulin A nephropathy.

IgA nephropathy (IgAN) is characterized by mesangial IgA deposition, and up-regulation of the IgA system is frequently described. This study investigated in vitro immunoglobulin isotype production by peripheral blood mononuclear cells from patients with IgAN and controls, without mitogenic stimulation and under the influence of cell cycle inhibitors and cyclosporin A (CyA). In controls, only IgM production was suppressed by cell cycle inhibitors, and no isotype was affected by CyA. This suppressible IgM production may represent antigen-independent 'natural antibody'. In IgAN, IgM, IgA and IgG were all suppressed by cell cycle inhibitors, and CyA suppressed IgA production. This state of altered immune activation in IgAN demonstrates T-cell-independent IgA production, suggesting that it is IgA 'natural antibody'. In conclusion, we suggest that mesangial IgA deposition may not be antigen dependent but due to some non-immune characteristic of the IgA molecule.

Adult↗

The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. I. Surface immunoglobulin isotypes on primed B cells in the spleen.

We investigated the ability of IgM-, IgD-, and IgG-bearing cells from the spleens of (BALB/c x C57BL/Ka)F1 mice primed to dinitrophenyl-bovine serum albumin (DNP-BSA) to restore the adoptive secondary anti-BSA and anti-DNP antibody responses. A rabbit anti-mouse IgD antiserum was prepared and the specificity documented by radioimmunoprecipitation, and cell surface staining. Purified populations of IgM-, IgD-, and IgG-bearing cells were prepared by immunofluorescent staining with isotype-specific reagents, and sorting on the fluorescence activated cell sorter. Bright or dull cells were transferred to irradiated syngeneic recipients which were challenged with DNP-BSA in saline. Unfractionated spleen cells restored an adoptive secondary serum antibody response which was all IgG (2-mercaptoethanol resistant). Purified IgM- or IgD-bearing cells restored both the secondary IgM and IgG antibody response. IgG-bearing cells restored only the IgG response. In addition, the IgG-bearing cells appear to suppress the adoptive secondary IgM response, since depletion of IgG-bearing cells from transferred spleen cells results in a marked increase in the adoptive IgM response.

Animals↗

Immunoglobulin isotypes in the circulating immune complexes of diabetic rats with and without proteinuria: a chronological study.

Circulating immune complexes (CIC) have been postulated to contribute to the development of the secondary complications of diabetes mellitus. Therefore studies were performed to determine whether CIC are the cause of the consequence of the development of diabetic nephropathy. This was done by comparing the occurrence and concentration of CIC containing the different isotypes of immunoglobulins in control rats to those detected in streptozotocin-induced (Sz) diabetic rats that developed albuminuria (Group I) and that did not develop albuminuria (Group II). Only CIC containing IgM, IgG2b and IgG2c were detected in diabetic rats. By staging Group I albuminuric diabetic rats to a clinical reference point of albuminuria, there was no correlation between the occurrence or concentration of CIC containing any isotype of immunoglobulin and the onset of albuminuria. In all Group I albuminuric diabetic rats, the occurrences of all CIC were variable and their concentrations fluctuated during the development and early progression of nephropathy. However, after this group of diabetic rats progressed to overt nephropathy (marked by albuminuria and IgG proteinuria), CIC could be demonstrated in 100% of the animals. In diabetic rats that did not develop albuminuria (Group II), CIC containing IgG2b occurred earlier and more often than in Group I albuminuric rats. Similarly, the subclass IgG2c was detected in the CIC of Group II non-albuminuric rats more frequently and in higher concentrations than in Group I albuminuric rats. CIC containing IgM were detected in all 3 animal groups, however, in higher concentrations and occurrences in Group II non-albuminuric rats as compared to control and Group I albuminuric rats. The consistent elevation in CIC after the development of diabetic nephropathy, suggests that the CIC containing any immunoglobulin isotype either result from diabetic kidney, or from other deteriorating conditions associated with the diabetic state. The data also suggests that CIC are not involved in the onset or progression of diabetic nephropathy regardless of the isotypes of immunoglobulins contained within the CIC. However, there is an isotypic restriction in the immunoglobulins detected in the CIC of diabetic rats (IgM, IgG2b and IgG2c) that may signal some involvement of the immune system in the development of diabetic nephropathy.

Albuminuria↗

Evidence for class-specific factors in immunoglobulin isotype switching.

Immunoglobulin class switch recombination (SR) occurs by a B cell-specific, intrachromosomal deletional process between switch regions. We have developed a plasmid-based transient transfection assay for SR to test for the presence of transacting switch activities. The plasmids are novel in that they lack a eukaryotic origin of DNA replication. The recombination activity of these switch substrates is restricted to a subset of B cell lines that support isotype switching on their endogenous loci and to mitogen-activated normal splenic B cells. The factors required for extrachromosomal plasmid recombination are constitutively expressed in proliferating splenic B cells and in B cell lines capable of inducibly undergoing immunoglobulin SR on their chromosomal genes. These studies suggest that mitogens that induce switching on the chromosome induce accessibility rather than switch recombinase activity. Finally, we provide evidence for two distinct switching activities which independently mediate mu-->alpha and mu-->gamma3 SR.

Animals↗

Genetic selection for high and low immune response in pigs: effects on immunoglobulin isotype expression.

Immunoglobulin (Ig) function varies by isotype and antibody activity is best mediated by isotypes most able to control the inciting infection. In pigs, a high ratio of IgG1:IgG2 is associated with resistance to disease caused by the extra-cellular bacterium Actinobacillus pleuropneumoniae. This ratio is controlled by type 1/type 2 cytokines in vitro, reflecting cell- (CMI) or antibody-mediated immune (AMI) responses, respectively. Animals were used which had been previously selectively bred for high (HIR) or low (LIR) combined AMI and CMI and had been immunized with hen eggwhite lysozyme (HEWL) in Quil A (days 0 and 14) while Bacillus Calmette Guérin was given on day 9. To test the hypothesis that lines do not differ in IgG isotype expression as antibody to HEWL, the ratio of anti-HEWL associated with IgG1 and IgG2 was determined at days 0, 9, 14 and 21. The ratio of IgG1:IgG2-associated antibody was always <1.0 indicating a type 1 response and differed significantly over time in HIR and LIR animals. After primary and secondary immunizations, the HIR animals' IgG1:IgG2-associated antibody ratio increased and approached 1 while for LIR animals the ratio decreased. Thus anti-HEWL antibody in HIR, but not LIR, approached balance in type 2:type 1 expression. Individual variation in immune response was frequently significant within each immune response group. Thus, proportional production of anti-HEWL antibody associated with IgG isotypes varies by individual and differs over time as a function of genotype in pigs selectively bred for HIR or LIR.

Animals↗

B1 cells contribution to susceptibility in experimental paracoccidioidomycosis: immunoglobulin isotypes and repertoire determination.

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. The experimental murine model has been used to approach the disease, with susceptible and resistant mice strains that reproduce most of the main human immunological features. Since the hypergammaglobulinemia observed in susceptible mice and humans might have an influence on B1 cells, we investigated its role during the experimental infection with Paracoccidiodes brasiliensis. CBA/Nxid mice, deficient in B1 cells, and CBA/Nxid reconstituted with B1 cells isolated from the non-mutant CBA/J strain were infected with 106 yeast forms of P. brasiliensis. At the 8th and 22nd week post infection the DTH response of CBA/Nxid mice was significantly higher after 24 h of P. brasiliensis antigens inoculation and the specific humoral response was reduced, in comparison to CBA/J or recCBA/Nxid. Production of NAbs is a hallmark of the B1 subset. Higher Ig productions to auto antigens such as DNA, MBP and RBC were observed in CBA/J infected mice or recCBA/Nxid. Anti P. brasiliensis IgG2a was produced by CBA/Nxid mice early in infection, while CBA/J or recCBA/Nxid presented increased levels of this isotype only after the 8th week of infection. Furthermore, western blotting analysis showed that CBA/Nxid mice expanded less clones against P. brasiliensis antigens, with weakly detectable anti-gp43 antibodies while CBA/J mice produce IgM anti-gp43 at the 2nd week of infection and IgG anti-gp43 at the 2nd and 8th week. On the other hand, recognition of gp70, a fungal antigen that, as gp43, inhibits macrophage activation was not compromised in B1 deficient mice. These results suggest that B1 cells might have influence in the kinetic of production of protective isotypes of immunoglobulins and their repertoire that could contribute to an early drive towards a Th2 response, affecting the cellular response in susceptible mice during experimental paracoccidiodomycosis.

Animals↗

Altered immunoglobulin isotype profile and anti-immature worm surface immunoglobulins in mice harboring a praziquantel-resistant Schistosoma mansoni isolate.

After placement in mice of PZQ-sensitive and -insensitive S. mansoni isolates obtained from villagers responding and not responding to PZQ, parasitological criteria reflecting their biological development and also the host anti-immature worm immunoglobulin isotypes were examined 8 and 10 weeks post infection. Hepatic granuloma diameter, hepatic histopathological changes and immunolocalization of IgG and IgM on the surface of PZQ-sensitive and -resistant worms were also examined 10 weeks post infection. Data showed that parasitological criteria were not significantly different between mice infected with the PZQ-sensitive and -insensitive S. mansoni isolates. As regards serum immunoglobulins, in mice infected with the PZQ-insensitive S. mansoni isolate, IgG and IgG1 were significantly (p<0.05) lower 8 and 10 weeks post infection, respectively (1.41+/-0.07 and 1.08+/-0.10 and 1.35+/-0.06 and 1.09+/-0.07) than in mice infected with the PZQ-sensitive S. mansoni isolate (1.73+/-0.15 and 1.38+/-0.10 and 1.73+/-0.17 and 1.54+0.21) after the same observation periods. IgM level was nearly the same while IgE was lower than that recorded in mice infected with the PZQ-sensitive S. mansoni isolate. IgG immunofluorescence was also lower (60%+/-6.78) on the surface of resistant worms than that of sensitive worms (66.6%+/-5.27); meanwhile, hepatic granuloma diameter was significantly larger (296.5+/-3.0 vs 283.6+/-4.0) in mice infected with the PZQ-insensitive S. mansoni isolate with higher percentage of intact eggs. Differences in the immunogenic make up of PZQ-sensitive and -insensitive S. mansoni isolates qualitatively and/or quantitatively favoring a certain Th cell subpopulation response could be the underlying reason for such differences recorded in the host immunoglobulin isotype response and also the egg-induced hepatic histopathological changes.

Animals↗

Immunoglobulin isotypes in childhood asthma.

Immunoglobulin isotypes (IgG, IgA, IgM, IgD, IgE) in serum were investigated in 64 Libyan children with mild to moderately severe asthma (age: 1-12 years; sex: 39 males, 25 females) (Group A) and in 57 healthy Libyan children (age: 1-12 years; sex: 30 males, 27 females (Group B). The patients were classified according to age into three groups (A1: 1-3 years; A2: > 3-5 years; A3: > 5-12 years); according to disease activity into two groups (AA: active disease; NA: inactive disease); and according to age plus disease activity into six groups (AA1, NA1; AA2, NA2; AA3, NA3). The healthy children were also divided according to age into three groups (B1: 1-3 years; B2: > 3-5 years; B3: > 5-12 years). IgG, IgA, IgM and IgD were measured by radial immunodiffusion method and IgE was estimated by enzyme immunoassay technique utilizing immunokits from bioMerieux, France. Serum levels of IgG, IgD and IgE were elevated significantly in patients compared to controls (A vs B: p < 0.05) while IgA and IgM levels were normal (p > 0.05). IgG and IgD levels were raised in A3 (p < 0.05), while IgD levels were raised in both A2 and A3 (p < 0.05) and IgE was elevated in all age groups (p < 0.05). However, IgG was elevated significantly in AA only, while IgD and IgE levels were high in both AA and NA (p < 0.05) and IgE was even considerably higher in AA compared to NA (p < 0.02). Further elevated levels were observed for IgG in AA3 only (p < 0.05), for IgD in NA2 (p < 0.01), AA3 (p < 0.01) and NA3 (p < 0.05) and IgE was much higher in patients with active disease than with inactive disease in all age groups (p < 0.05). The fact that asthmatic attack in majority of our patients can be explained as mediated through IgE and the possibilities that IgG and IgD may play roles as aetiopathogenetic or protective regulatory factors in childhood asthma are discussed.

Age Factors↗

Monoclonal antibodies against porcine immunoglobulin isotypes.

Monoclonal antibodies (MCAs) against porcine immunoglobulin isotypes* G, G1, G2, M and A have been produced and characterized in detail. Epitope analysis using a competitive direct enzyme-linked immunosorbent assay (ELISA) indicated that the MCAs recognized 3 class-specific epitopes of IgG, 4 epitopes specific for IgG1, 3 epitopes specific for IgG2, 2 epitopes of IgM and 2 epitopes of IgA. Two MCAs against IgG2 were shown to react with an allotypic determinant (B2) and one MCA against IgM is probably allotype specific. The production of MCAs specific for IgG and for its subclasses G1 and G2 and, in addition, the one-step isolation of nearly pure IgG1 and IgG2 preparations by immunoaffinity chromatography using MCA 34.1.1a (anti-IgG2) confirmed the existence of at least two subclasses of IgG. Preliminary results further suggested the existence of a subpopulation of IgG1 which could be eluted selectively from Protein A-Sepharose columns at pH 5.0. MCA 34.17.2a appeared to react preferentially with this IgG1 subpopulation and could be used to isolate a similar IgG1 subpopulation by immuno-affinity chromatography. Several of the MCAs have been successfully applied for the detection of porcine immunoglobulin isotypes by a double antibody sandwich ELISA and for the (isotype-specific) detection of antibodies against various porcine viruses. The availability of a full set of MCAs against porcine immunoglobulin isotypes will stimulate and facilitate the further study of the porcine immune system.

Animals↗

Immunoglobulin isotype distribution of antinuclear antibodies in dogs with leishmaniasis.

A modified indirect immunofluorescence method, using rat liver as substrate, was developed to determine the immunoglobulin isotypes forming antinuclear antibodies in sera from 12 antinuclear antibody-positive dogs out of 121 dogs with natural Leishmania infection. Immunoglobulin M was found to be the most frequent component of antinuclear antibodies (91.7 per cent), followed by IgG (41.7 per cent) and IgA (33.2 per cent). When these immunoglobulin isotypes were titrated, IgG antinuclear antibodies showed higher titres (1:200) than IgM and IgA antinuclear antibodies (1:50 and 1:20 respectively). Most of the antinuclear antibody-positive dogs simultaneously had two immunoglobulin isotypes, whereas none had all three immunoglobulin isotypes at the same time. Spearman rank correlation analysis showed no significant correlation between antinuclear antibody titres and circulating immune complexes or immunoglobulin levels. The low incidence of antinuclear antibodies and the absence of a clear relationship between isotype titres and clinical signs suggest a minor pathogenic role of antinuclear antibodies in canine leishmaniasis.

Animals↗

Proportions of immunoglobulin isotypes in paralytic poliomyelitis and after vaccination.

Immunoglobulin isotype composition of poliovirus antibodies was studied by isotype-specific solid-phase radio-immunoassay (RIA) in four patients with paralytic poliomyelitis, five adults receiving live poliovirus vaccine as a booster immunization, and seven children receiving first doses of inactivated poliovirus vaccine. In paralytic poliomyelitis serum and cerebrospinal fluid (CSF) poliovirus antibodies were mainly of IgG1, IgG3, and IgA isotypes. IgM antibodies were found in sera but not in CSF. Either IgG2 and IgG4 antibodies were undetectable or the titers were low. In adults who had received live trivalent poliovirus vaccine, antibodies against poliovirus type 3 were detected in IgG1 (53% of total antibodies), IgG3 (25%), IgM (9%), IgA (8%), IgG2 (3%), and IgG4 (2%) isotypes. In prevaccination and late postvaccination sera the share of IgG3 antibodies was exceptionally high (35%). In children who received inactivated poliovirus vaccine, antibodies developed in IgG1 (53-61% of total antibodies for poliovirus types 1, 2, and 3), IgG3 (12-21%), and IgM (23-33%) isotypes. Antibody levels in IgG2, IgG4, and IgA isotypes were low and observed only in a few cases. Like other viral antibodies IgG1 and IgG3 isotypes were the major IgG subclasses in poliovirus antibodies.

Adult↗

Progression to type 1 diabetes is associated with a change in the immunoglobulin isotype profile of autoantibodies to glutamic acid decarboxylase (GAD65). Childhood Diabetes in Finland Study Group.

To investigate whether type 1 diabetes in man is associated with a preferential Th1/Th2 response, and whether autoantibodies to one of the main autoantigens would reflect such a response, we characterized the immunoglobulin isotype profile to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) in siblings to IDDM patients. Samples obtained from affected subjects before and at clinical onset of IDDM, from unaffected individuals at high risk and at low risk and from healthy controls were studied. The immunoglobulin isotype profile in the siblings at low risk reflected a more immature, i.e., IgM and Th2 like, i.e., IgE response compared to the progressors and siblings at high risk, with significantly higher median levels of IgM and IgE. The rank order of anti-GAD65 immunoglobulin isotypes was similar in the siblings before and at clinical onset of IDDM, IgG1 > IgG4 > IgM > IgE > IgA > IgG3 > IgG2, but markedly different in the individuals at low risk, IgG1 > IgM > IgE > IgG4 > IgG3 > IgA > IgG2. Based on these observations, we suggest that progression to clinical onset of IDDM is associated with a maturation and a decrease in the Th2 immune response against GAD65; findings which could have implications for future intervention and prediction strategies.

Adolescent↗

Distribution of immunoglobulin isotypes and subisotypes in equine guttural pouch (auditory tube diverticulum).

To clarify the functions of the equine guttural pouch, the distribution of various immunoglobulin isotypes and subisotypes in the guttural pouch mucosa were examined in healthy horses. IgGa was present in the mucosa of guttural pouch, mucosal lymph nodules and submucosal lymph nodules. IgM was scattered in the mucosal lymph nodules and in the germinal centers of the submucosal lymph nodules. IgGc was recognized only in the submucosal lymph nodules. These immunoglobulin isotypes and subisotypes were found in lymphocytes and plasma cells. On the other hand, IgA was detected in glandular epithelial cells and the surface layer of the mucosal epithelium, as well as in free cells. This finding suggests that IgA is secreted through the glandular epithelium. Based on the above findings, we conclude that the guttural pouch has phylactic ability.

Animals↗

Brucella abortus-specific immunoglobulin isotypes in serum and vaginal mucus from heifers vaccinated with Brucella abortus salt-extractable proteins and challenge exposed with virulent Brucella organisms.

Serum and vaginal Brucella-specific immunoglobulin isotypes (IgG1, IgG2, IgM, and IgA), obtained from 62 crossbred beef heifers vaccinated with Brucella abortus salt-extractable proteins and subsequently challenge exposed with B abortus S2308, were studied. Brucella-specific IgG antibodies and Brucella-specific immunoglobulin isotypes were quantitated by a fluorometric immunoassay. Serum and vaginal immunoglobulin responses were evaluated as a method of distinguishing infected from noninfected heifers. Rivanol precipitation, complement-fixation, buffered-antigen brucellosis tests and an ELISA were performed on sera. For immunoglobulin isotypes, vaccinated heifers had mean antibody responses higher than baseline mean antibody responses for at least 31 weeks after vaccination. After challenge exposure, significant differences (P greater than 0.05) were not detected between mean antibody responses of vaccinated and nonvaccinated heifers. Vaginal Brucella-specific antibody responses did not correlate with protection from disease. Vaginal Brucella-specific IgM was detected only at the time of abortion. Vaginal IgA appeared specific for identification of virulent B abortus infection. All serotests appeared adequate in distinguishing baseline titers from titers of heifers that had aborted and were considered bacteriologic culture-positive. Results of serotests neither consistently distinguished vaccinates from challenge-exposed cattle nor distinguished heifers that were challenge exposed, had aborted, and were considered bacteriologic culture-positive adequately from heifers that were challenge-exposed, had not aborted, and were considered bacteriologic culture-negative. Brucella-specific IgA appeared to be the most effective in distinguishing vaccinated heifers from challenge- exposed heifers and heifers that were challenge exposed and had aborted, from heifers that were challenge exposed and had not aborted. Brucella-specific serum IgA was detected up to 13 weeks after abortion.

Animals↗

Bacterial lipopolysaccharide causes variable deposits of diverse immunoglobulin isotypes in kidneys of lupus-prone mice.

We investigated the role of immunoglobulin isotypes in the exacerbation of lupus nephritis associated with exposure to bacterial lipopolysaccharide. The data indicate that enhanced polyclonal B-cell activation and exacerbated autoimmune disease evoked by lipopolysaccharide are associated with an increase in the concentration of isotypes in plasma and in renal eluate, that this isotype response is polyclonal and preferential but not restrictive, that all B cells are responsive but all are not equally sensitive to the effects of lipopolysaccharide, and that some expanded isotypes may be more nephritogenic in certain strains of lupus-prone mice.

Animals↗