Loss of antibody production accompanied by chromosome loss in a cloned hybrid line secreting antibodies to sheep red blood cells

Summary Somatic cell hybrids between Sp2/O-Ag14 mouse myeloma cells and lymphocytes derived from BALB/c mice hyperimmunized with sheep red blood cells (SRBC) were produced. One hybrid producing IgG₁ antibody to SRBC was selected, cloned twice and subsequently transferred to BALB/c mice. After a number of transfers it was found that the antibody titer in ascitec fluid gradually decreased. Cytogenetic analysis revealed gradual chromosome loss in the hybrid clone, which produced progressively less antibody.     

Vitamin C and the immune response.

The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.     

Vitamin C and the immune response

Summary The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.We thank Miss Wendy Treat for excellent technical assistance.     

Effects of cadmium on the immune system of mice.

Chronic oral exposure of mice to Cd++ inhibits cell-mediated immunity of delayed type hypersensitivity induced by sheep red blood cells (SRBC). No effect was detected on humoral immune response to SRBC. Spleen cells derived from mice exposed to Cd++ showed in vitro enhanced response to T and B cell mitogens. These results demonstrate that Cd++ exposure alters the immune system of mice.     

Production of monoclonal anti-Schistosoma mansoni antibodies. Preliminary study of their biological activities]

Monoclonal antibodies against Schistosoma mansoni have been produced by fusion of splenic lymphocytes from S. mansoni infected Rats and P3-X63-Ag8 BALB/c cells. In vitro and in vivo studies of the biological activities of these antibodies have led to the identification of IgE antibodies with a high reaginic activity and antibodies which in a complement dependent or eosinophil dependent system were shown to have a marked cytotoxicity for schistosomula in vitro. This methodology seems to open new perspectives for the study of antibody function in immunity against parasites as well as for the isolation of the corresponding target antigens.     

Effect of synthetic polynucleotides on the growth of transplantable tumours in BALB/c mice.

The effect of BALB/c mice pretreatment with tumour cells (a mammary adenocarcinoma, ADK-1t and an IgA secreting plasmocytoma, MOPC-315) adsorbed with poly I:C, poly I and poly C is examined. Only mice pretreated with cells of both tumours adsorbed with poly I:C and poly C proved to be extensively protected against challenge by homologous untreated tumour cells, whereas this was not so in the case of poly I. A possible explanation of this phenomenon is discussed.     

Somatic cell hybrids producing inhibitors of melanotic melanoma tyrosine hydroxylase

Summary Splenic lymphocytes from BALB/c mice pre-immunized with purified tyrosine hydroxylase (TH) were fused with murine myeloma N/1 cells. Supernatants of only 2 from large number of cloned cell hybrids contained an inhibitor of TH.     

Effect of synthetic polynucleotides on the growth of transplantable tumours in BALB/c mice

Summary The effect of BALB/c mice pretreatment with tumour cells (a mammary adenocarcinoma, ADK-1t and an IgA secreting plasmocytoma, MOPC-315) adsorbed with poly I:C, poly I and poly C is examined. Only mice pretreated with cells of both tumours adsorbed with poly I:C and poly C proved to be extensively protected against challenge by homologous untreated tumour cells, whereas this was not so in the case of poly I. A possible explanation of this phenomenon is discussed.This work was supported by a research contract with the Italian National Research Council (C.N.R.).     

Effects of cadmium on the immune system of mice

Summary Chronic oral exposure of mice to Cd⁺⁺ inhibits cell-mediated immunity of delayed type hypersensitivity induced by sheep red blood cells (SRBC). No effect was detected on humoral immune response to SRBC. Spleen cells derived from mice exposed to Cd⁺⁺ showed in vitro enhanced response to T and B cell mitogens. These results demonstrate that Cd⁺⁺ exposure alters the immune system of mice.Dedicated to Prof. Georg Henneberg on the occasion of his 70th anniversary on 12.10.1978.Acknowledgments. Supported by a grant from the Umweltbundesamt. We thank Ms Odenwald, Ms Schulz, Klinikum Steglitz, and Ms Emeis, Robert Koch-Institut Abt. Immunologie, for the excellent technical assistance.     

Drug susceptibility of PCA in WBB6F1-W/Wv mice

Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be produced in congenitally mast cell-deficient WBB6F1-W/W^v (abbreviated as W/W^v) mice on sensitization with undiluted or slightly diluted allogeneic and xenogeneic antisera but not on sensitization with allogeneic monoclonal immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration [1]. In view of these findings, the present study was conducted to characterize PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1-+/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/W^v mice mediated by a low dilution (1  4) of hyperimmune serum to bovine serum albumin of the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of platelet-activating factor (PAF), but not by antihistamines such as cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by a high dilution (1  128) of the anti-serum (virtually by IgG1 antibody) was nearly completely suppressed by antihistamines but not by CV-6209. A remarkable difference between PCA in W/W^v and reference mice was also observed in the susceptibility to monoclonal anti mouse granulocyte (Gr-1) antibody PCA in W/W^v mice was potently suppressed by the 1- to 3-day pretreatment with this antibody but that in references was not at all. Putting these present results together with the previous finding that anti-granulocyte antibody greatly reduces circulatory Gr-1⁺ leukocytes, 1 to 3 days after the treatment [2], it is highly probable that PCA in W/W^v mice mediated by some antibody isotypes other than IgE and IgG1 is produced by PAF mainly released from Gr-1⁺ cells, while IgG1 antibody-mediated PCA in mast cell-bearing reference mice is evoked by histamine derived from mast cells. PCA homologous to that in W/W^v mice could also be produced in the reference mice on sensitization with undiluted or slightly diluted antiserum, when generalized blueing due to excess IgG1 antibody was removed by the oxatomide treatment be fore the antigen challenge. Received 10 December 1997; received after revision 2 February 1998; accepted 23 February 1998     

Effect of chronic administration of morphine on primary immune response in mice

Summary The effect of 3 different doses of chronically-administered morphine on the primary immune response was studied in mice by estimating spleen/body weight ratio and serum hemolysin production against sheep red blood cells (SRBC). It was observed that morphine exerted a dose-dependent inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. The findings suggest that the inhibitory effect of morphine is specific.     

Inhibition of antigenic competition by immunostimulants]

The diminution of immune response against SRBC induced in mice, by a prior injection of HRBC was counteracted by addition of certain immunostimulants to SRBC. The intensity of inhibition of antigenic competition was related to the quantity of immunostimulant added to SRBC. Some immunostimulants (B. abortus, lipopolysaccharide) were more active than others (C. parvum, Poly I : C). To inhibit antigenic competition immunostimulant had to be injected after or in mixture with SRBC never before.     

Production of passive cutaneous anaphylaxis (PCA) and reversed PCA by rat IgE antibody in the mouse

Although IgE antibody is generally characterized as a homocytotropic antibody, it has been well known for some time that mouse IgE antibody causes potent sensitization of rat skin for PCA. The present study clearly shows the reciprocal cross-sensitization of mouse skin with rat IgE molecules. PCA and RPCA were produced by rat IgE antibody in an inbred mouse strain. DS/Shi, though not in C3H/HeShi, C57BL/6JShi and BALB/cCrj strains. Sensitization of DS/Shi mouse skin for PCA with rat IgE antibody was comparable in sensitivity with that of rat skin, but lasted only for a short term in comparison with the long persistence in rat skin.     

Haemopoietic stem cell concentration and CFUs in DNA synthesis in bone marrow from different bone regions

Summary The concentration of colony-forming cells (CFUs) is about 40% less in sternal marrow than in the marrow of lumbar vertebrae and femora. Marrow of trabecular bones in lumbar vertebrae contains fewer mitotically active CFUs than marrow of trabecular bones in the femoral distal epiphysis and metaphysis, or the peripheral marrow near the cortical bone in the femoral diaphysis. Only a minor part of the variability of the results in the CFU-assay is due to differences in CFU-concentrations between individual donor mice; pooling of the cell suspensions does not substantially decrease variability. Specific pathogen-free mice yield the same results as BALB/c mice from conventional breeding.Acknowledgments. This work was performed with support of Euratom contract No. 233-771 BIO B. We thank L. Tessens for his excellent technical assistance.     

Production of passive cutaneous anaphylaxis (PCA) and reversed PCA by rat IgE antibody in the mouse

Summary Although IgE antibody is generally characterized as a homocytotropic antibody, it has been well known for some time that mouse IgE antibody causes potent sensitization of rat skin for PCA. The present study clearly shows, the reciprocal cross-sensitization of mouse skin with rat IgE molecules. PCA and RPCA were produced by rat IgE antibody in an inbred mouse strain, DS/Shi, though not in C3H/HeShi, C57BL/6JShi and BALB/cCrj strains. Sensitization of DS/Shi mouse skin for PCA with rat IgE antibody was comparable in sensitivity with that of rat skin, but lasted only for a short term in comparison with the long persistence in rat skin.     

Vitamin A and tumor immunity

Summary Intraperitoneal administration of vitamin A into the BALB/c mice inoculated with a syngeneic fibrosarcoma, Meth A, caused a remarkable augmentation of tumor rejection. A cell-depletion technique revealed that the primary effector cells responsible for the augmented rejection were Thy-1 positive, Lyt-1 negative, Lyt-2 positive lymphocytes, suggesting the involvement of cytotoxic lymphocytes.This work was supported in part by a Grant-in-Aid for scientific research from the Ministry of Education, Science and Culture, Japan, and in part by a Grant-in-Aid for cancer research from the Fukuoka Cancer Society, Japan.We thank Mr M. Fujiki and Miss A. Maeda for excellent technical assistance.     

Effect on non-steroidal anti-inflammatory drugs on Moloney sarcoma virus inoculated mice

Summary Chronic administration of phenylbutazone, flufenamic acid and a new, potent non-steroidal anti-inflammatory agent ITF (3-methyl-5-benzoyl-amino-isothiazole-4-carboxy-p-ethoxyphenylamine) to BALB/c mice inoculated with a Moloney sarcoma virus resulted in a stimulation of tumor growth and increased severity of disease. This treatment, however, had no effect on the spontaneous regression of tumors. Indomethacin in a dose of 5.0 or 2.5 mg per kg suppressed the MSV-induced tumor growth, but this effect was apparently connected with the high toxicity of this drug for mice.     

Tumor incidence in Visna virus inoculated mice.

Mice (female Swiss albino) inoculated when newborn with Visna virus had tumors in 77% of cases when examined 8-12 months later. The tumors were mainly of the mammary carcinoma type. The tumor incidence in non-infected control animals was only 20%. In contrast, no increased incidence of tumors was observed among Visna virus-inoculated inbred mice (BALB/c, CBA and DBA) with low incidence of spontaneous mammary carcinoma.     

Number of dopamine neurons predicts prolactin levels in two inbred mouse strains

Summary Mice of the BALB/cJ strain have more dopamine neurons than mice of the CBA/J strain. We now report that BALB/cJ mice have less circulating and pituitary prolactin than CBA/J mice, a relationship expected from the difference in tuberoinfundibular dopamine neuron number.