Interaction of antigen load and antibody response in determining heterologous protein nephritogenicity in inbred mice

Genetically disparate inbred mouse strains mounting quantitatively different immune responses to a potentially nephritogenic heterologous protein had varied development of glomerulonephritis (GN) dependent upon the interaction between level of antibody response and antigen dose. High responder BALB/c mice given high doses of horse apoferritin developed a severe necrotizing GN. BALB/c mice given low dose horse apoferritin developed less severe GN, or when antibodies were in extreme excess, no GN. Low responder C3H mice given high dose horse apoferritin were in extreme antigen excess and developed no GN. C3H mice given low dose horse apoferritin developed a glomerulopathy characterized by capillary loop immune deposits. Interstrain differences in immune clearance and avidity did not account for this varied nephritogenicity, although avidity did relate to glomerular site of immune deposits in the BALB/c model. In the models under consideration susceptibility to heterologous antigen-induced glomerular injury was a function of the magnitudes of both the antibody response and the antigenic challenge.     

Interstrain peculiarities of the secondary immune response in mice

CBA, CC57BR, C57B1/6, BALB/c, and outbred white mice were intraperitoneally or subcutaneously (C57B1/6 strain) immunized with sheep red cells in a dose optimal for the development of delayed-type hypersensitivity but subthreshold for antibody production. Seven days later the mice were reimmunized with sheep red cells in various doses subcutaneously (CBA, C57B1/6, BALB/c, outbred mice) or intraperitoneally (CBA, CC57BR, outbred mice), and 5 days after reimmunization the intensity of antibody production and delayed-type hypersensitivity was assessed. Intact mice were controls. The immunization was found to selectively enhance delayed-type hypersensitivity in C57B1/6, CC57BR, and BALB/c mice and to intensify antibody production in CBA mice; both phenomena were observed in outbred mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 499–501, November, 1994 Presented by K. P. Kashkin, Member of the Russian Academy of Medical Sciences     

Homologous and heterologous protection of mice with group A streptococcal M protein vaccines.

Purified streptococcal M proteins precipitated with alum (APM) were used to immunize mice. A trivalent vaccine of serotypes 1, 3, and 12 protected mice against challenges by homologous live streptococci and also conferred protection against serotypes 6 and 14 but not against a strain of group B streptococci. Monovalent APM vaccines afforded homologous protection and restricted heterologous protection. The extent of heterologous protection was a function of serotype combinations and was also dose dependent. Rabbit antisera exhibiting strong opsonic activities were active in vitro and in passive mouse protection only for homologous serotypes. Mouse antisera did not passively transfer protection and were not bactericidal in vitro. It was concluded that homologous and heterologous active mouse protection was most likely a result of shared antigenic determinants of the various M proteins although protection of mice could not be measured as a function of circulating anti-M antibodies.     

Diurnal variations in mitotic activity in mice

Summary A study was made of the regularities in the 20-hour changes in the mitotic activity of intestinal epithelium of the salivary glands, pancreas, kidney, epidermis and corneal epithelium of mice. Changes of the functional activity of these organs were recorded simultaneously. Regular 24-hour changes of mitotic activity were noted in various test organs. The 24-hour mitotic rhythm curves had two peaks in the case of digestive organs: in case of the kidney the curves were also double-peaked, the peaks, however, being less marked. The second peak of the cellular mitotic activity curve is connected with the regimen of the animal feeding. The curves of the 24-hour rhythm of the number of mitoses had a single peak in the case of corenal epithelium and epidermis. In the 24-hour changes of the cellular mitotic activity there existed a reverse relationship between the number of dividing cells and the functional activity of the organ.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 53, No. 4, pp. 100–104, April, 1962     

Interstrain differences of ionotropic glutamate receptor subunits in the hippocampus and induction of hippocampal sclerosis with pilocarpine in mice

Rodent strains used in epilepsy research have various neurological characteristics. These differences were suggested to be attributed to the diverse densities of the ionotropic glutamate receptor (iGluR) subunits. However, previous studies failed to find interstrain differences in the hippocampal receptor levels.We supposed that a detailed layer-to-layer analysis of the iGluR subunits in the hippocampus might reveal strain-dependent differences in their base lines and reactions induced by pilocarpine (PILO) between two mouse strains without documented ancestors.Levels of iGluR subunits in Balb/c and NMRI mice were compared using semiquantitative immunohistochemistry. The alterations in the neuronal circuitry were validated by neuropeptide Y (NPY) and neuronal nuclear antigen (NeuN) immunostainings.Immunohistochemistry showed interstrain laminar differences in some subunits of both the control and PILO-treated animals. The seizure-induced irreversible neuronal changes were accompanied by reduced GluA1 and GluA2 levels. Their changes were inversely correlated in the individual NMRI mice by Pearson's method. Increase in NPY immunoreactivity showed positive correlation with GluA1, and negative correlation with GluA2. The NMRI strain was susceptible to PILO-induced hippocampal sclerosis, while the Balb/c animals showed resistance.Basal levels of iGluRs differ in mouse strains, which may account for the interstrain differences in their reactions to the convulsant.     

Interstrain cross-reactive idiotypes on monoclonal antibodies to an encephalitogenic myelin basic protein peptide.

In order to assess the role of idiotype (Id) and the anti-Id network in murine experimental autoimmune encephalomyelitis (EAE), Id-bearing monoclonal antibodies (mAb) to human myelin basic protein (MBP) peptide acetyl 1-9, as well as mAb anti-Id, were developed in EAE-susceptible PL/J mice (H-2u). These mice recognize MBP residues acetyl 1-9 as an encephalitogenic determinant. Reactivities of PL/J Id-bearing mAbs to MBP and to MBP peptides were identical to those of mAbs generated against the same MBP peptide in EAE-resistant BALB/c mice (H-2d), even though isotypes of the mAbs differed. By using an inhibitory ELISA and immunoblotting, it was demonstrated that one PL/J mAb anti-Id recognized a public or framework Id, whereas another PL/J mAb-anti Id was directed to a private Id more restricted to the paratopic site. Two Id-bearing PL/J mAbs shared a cross-reactive Id (IdX) on the light chain, and an interstrain IdX was present on both the heavy and light chains of mAbs raised in PL/J and BALB/c mice to the same MBP peptide. The PL/J mAb anti-Id was capable of cross-regulating the production of Id-bearing mAbs by hybridomas across murine strains. These findings suggest that a restrictive family of germ-line genes encode for these Id-bearing antibodies to MBP peptide, irrespective of whether the MBP peptide is encephalitogenic in the murine strain immunized. Manipulation of the Id network may provide a means for modifying autoimmune demyelinating diseases of the central nervous system.     

Studies on rotavirus homologous and heterologous active immunity in infant mice

Homologous and heterologous active immunity was studied in mice with mammalian group A rotaviruses. One day old mice were vaccinated with one of the following rotaviruses: bovine B641 (serotype 6), bovine B223 (untyped), simian SA11 (serotype 3) and murine EDIM (untyped). At 10 days of age they were challenged with EDIM virulent virus or SA11 virus. All the vaccines induced a serological antibody response in the mice but only the homologous immune response was protective.     

Interstrain variability of larval photokinesis inDrosophila melanogaster

Larvae from seven laboratory strains and eight isofemale lines ofDrosophila melanogaster differ significantly with regard to their responses to light in a photokinesis assay in which the larvae are tested en masse. Larvae from the CA-2 laboratorystock fail to disperse on assay plates, although observations of individual CA-2 larvae suggest that the larvae are repelled by light. Larvae from all of the other laboratory stocks and all of the isofemale lines (except LI2 and NC5) avoid light in the photokinesis assay. Larvae from some stocks are much more strongly repelled by light than larvae from other stocks. LI2 larvae are unresponsive to light in most replicates of the photokinesis assay, while NC5 larvae are consistently unresponsive to light. Observations of F₁ heterozygotes suggest that the allele(s) that affects the vision of LI2 and NC5 larvae has net effects on the animals' behavior that are partially dominant and recessive, respectively.     

Immunization of BSVS mice with heterologous and homologous adrenal gland

Mice of the BSVS strain were immunized intracutaneously with bovine and intracutaneously and intraperitoneally with homologous adrenal homogenates in complete Freund's adjuvant. Immunization with bovine adrenal elicited the production of antibodies directed against an adrenal-specific antigen restricted to the bovine species as well as non-organ specific antibodies directed against the bovine species. These organ-specific antibodies directed against the bovine species. These organ-specific antibodies were demonstrated by passive haemagglutination, gel precipitation and immunoelectrophoresis. Antisera against bovine adrenal reacted stronger with antigen extracts prepared from the cortico-medullary junction than with extracts of isolated medulla or outer cortex indicating that the adrenal antigen may be located primarily in the cortical zona reticularis. Immunization with mouse adrenal did not elicit production of antibodies reactive with murine or bovine adrenal, or histological lesions in the adrenal gland.     

Independence of the nephritogenicity of group A streptococci from their M types

Fluorescein labelled IgG fractions of serum from patients with acute post-streptococcal glomerulonephritis (AGN) stained the glomerular basement membrane of renal tissue from the same and other patients with AGN obtained during the early phase of the disease. Using a spectrofluorometric method it was quantitatively shown that the staining capacity of these serum fractions was reduced after they had been preabsorbed with disrupted nephritogenic group A streptococci (type 12, 49 and a non-typeable strain) or their isolated plasma membranes. No such effect was observed when group A streptococci of types 3, 4, 6, 12, 14 and 25 or their plasma membranes obtained from patients without AGN were used for preabsorption. Plasma membranes of the nephritogenic type 12, 49 and the nontypeable strain diminished the staining capacity of the patients' labelled IgG fractions significantly, regardless of the serotype of the original nephritogenic streptococci isolated from the individual patient. These results indicate the presence of specific nephritogenic, type independent antigens in the plasma membrane of certain group A streptococci which appear to be shared by different serotypes.     

Bovine adenovirus type 3 containing heterologous protein in the C-terminus of minor capsid protein IX

Earlier, we detected pIX of BAdV-3 as a 14-kDa protein in purified virions. Analysis of BAdV-3 pIX using different region antibodies revealed that the N-terminus and central domain of the pIX contain immunogenic sites and are not exposed on the surface of BAdV-3 virion. This suggested that the C-terminus of BAdV-3 pIX (125 amino acid) may be exposed on the virion and may be used as a site for incorporation of heterologous peptides or proteins. We constructed recombinant BAV950 containing a small peptide (21 amino acid), including the RGD motif or recombinant BAV951 containing enhanced yellow-green fluorescent protein (EYFP) fused to the C-terminus of pIX. Western blot analysis demonstrated that the chimeric pIX-RGD was incorporated into virion capsids. Incorporation of the RGD motif into the pIX resulted in significant augmentation of BAdV-3 fiber knob-independent infection of the integrin-positive cells, suggesting that RGD motifs are displayed on the surface of virion capsids and are accessible for binding to integrins. Analysis of BAV951 revealed that the chimeric pIX is incorporated into virion capsids and EYFP containing the C-terminus of pIX is exposed on the surface of the virion. Moreover, insertion of chimeric pIXs was maintained without change through successive rounds of viral replication. These results suggested that in contrast to major capsid proteins (hexon, penton, fiber), the minor capsid protein IX can be use for the incorporation of targeting ligands based on either small peptides or longer polypeptides.     

The specificity of heterologous antiserum against brain of nude mice.

Serum prepared in rabbits against brain of nude mice was tested for its T-cell specificity by immunoperoxidase staining. The difference in activity of this anti-brain serum against early precursors and more differentiated precursors of the haemopoietic cell lines was investigated by CFU-s and CFU-c determination after serum incubation. The results showed that the activity of the anti-nude brain serum is completely comparable to serum prepared against brain of normal mice.     

The leukocytic reactions of irradiated mice to transfusion with heterologous blood

Summary Heterologous blood was transfused to intact and previously irradiated rats, the periods between irradiation and transfusion being 6 hours, 3 days, 4 and 8 weeks. For 6 hours after the transfusion a study was made of the dynamic reaction of leukocytes, neutrophiles and lymphocytes in the peripheral blood of these animals. Some postirradiation peculiarities attendingposttransfusional acute leukocytic reactions were revealed.(Presented by Active Member of the AMN SSSR V. Kh. Vasilenko) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 9, pp. 58–62, September, 1962     

Stimulation of anti-hapten response by heterologous protein devoid of hapten

Rabbits were immunized with dinitrophenylated proteins. Injections with heterologous proteins were given 11 to 25 days after the primary injection. Spleen cell suspensions from the immunized animals were exposed to either (a) the original antigen, (b) the carrier protein of the original antigen (c) the heterologous protein used for the second injection, and (d) the heterologous protein after it was dinitrophenylated. In all the experiments a significant increase in the anti-dinitrophenyl response was obtained, whereas no such response was obtained with proteins (or their dinitrophenylated derivatives) to which the animals were not previously exposed. The results suggest that the anti-hapten response can be significantly augmented by immunization with heterologous hapten-devoid proteins.     

The frequency of heterologous synapsis increases with aging in Robertsonian heterozygous male mice

The house mouse is characterised by highly variable chromosome number due to the presence of Robertsonian (Rb) chromosomes. During meiosis in Rb heterozygotes, intricated chromosomal figures are produced, and many unsynapsed regions are present during the first prophase, triggering a meiotic silencing of unsynapsed chromatin (MSUC) in a similar mode to the sex chromosome inactivation. The presence of unsynapsed chromosome regions is associated with impaired spermatogenesis. Interestingly, in male mice carrying multiple Rb trivalents, the frequency of germ cell death, defective tubules, and altered sperm morphology decreases during aging. Here, we studied whether synapsis of trivalent chromosomes and MSUC are involved in this improvement. By immunocytochemistry, we analysed the frequency of unsynapsed chromosomes and of those positive to γH2AX (a marker of MSUC) labelling in spermatocytes of 3-, 5- and 7-month-old Rb heterozygotes. With aging, we observed a decrease of the frequency of unsynapsed chromosomes, of spermatocytes bearing them and of trivalents carrying γH2AX-negative unsynapsed regions. Our quantitative results show that both synapsis and MSUC processes are better accomplished during male aging, partially accounting for the improvement of spermatogenesis.