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M Cohn

Publications and source records attributed to M Cohn.

At least 73 records · Page 4Linked to original sources
PubMed1986

The WI-L2-729-HF2 human hybridoma system. Arrangement of lambda genes in monoclonal hybrids.

Fusion of WI-L2-729-HF2 human lymphoblastoid cells and human B-cell blasts provides a very efficient and rapid means of isolating stable B-cell hybridomas that secrete high levels of new human immunoglobulins. By titrating the plating density of fused cells into microwells immediately following fusion, it has been possible to obtain monoclonal hybrids. In this communication, proof of monoclonality is provided based on subcloning, karyotyping, and Southern blot analyses of lambda light chain immunoglobulin genes. The results reveal rearranged lambda genes in hybridoma subclones that produce both kappa (the WI-L2-729-HF2 isotype) and new lambda light chains. In contrast, the WI-L2-729-HF2 parental cell line and kappa-producing hybrids exhibit a germline configuration of lambda genes. The results provide evidence that stable, monoclonally derived hybridomas may be obtained upon initial plating of fused cells, without subsequent subcloning. The data further demonstrate the WI-L2-729-HF2 system to be ideal for rapidly generating, at very high frequency, clonal human B-cell hybridomas that stably secrete human monoclonal antibodies.

B-Lymphocytes↗
PubMed1986

Injury to the eleventh cranial nerve in a high school wrestler.

Injury to the 11th cranial nerve is not uncommon and is usually associated with surgical procedures in the posterior triangle of the neck. Although palsy resultant from external trauma has been described, there have been no cases reported of this injury occurring in a wrestler. This paper reports on such a case and reviews both the anatomic and the clinical aspects of 11th-nerve palsy.

Accessory Nerve↗
PubMed1986

In vivo or in vitro selection for resistance to natural cytotoxic cell lysis selects for variants with increased tumorigenicity.

Experiments were designed to test the hypothesis that transformed cells that are NC sensitive must escape NC activity if they are to grow as tumors in normal individuals. NC-resistant variants were selected either in vivo or in vitro from NC-sensitive cell lines that grow as tumors in immunodeficient mice but not in syngeneic normal mice. The tumorigenicity of cloned NC-resistant variants was compared with the parental cell lines and to cell lines that went through the selection procedure, but after cloning remained NC sensitive. Cloned NC-resistant cell lines derived from tumors that developed in x-irradiated nude mice after the injection of an NC-sensitive cell line are tumorigenic in normal mice, whereas cloned NC-sensitive cell lines derived from the same tumors are unable to grow as tumors in normal mice. Similarly, six of seven NC-resistant cloned cell lines independently isolated after in vitro selection for NC-resistance are tumorigenic in normal mice, whereas cloned NC-sensitive cell lines isolated from the same in vitro selected populations are not tumorigenic in normal mice. Thus, either the in vivo or in vitro selection of NC-resistant cells selects for cells tumorigenic in normal mice; these findings, along with our previous observations that selection for cells tumorigenic in normal mice selects for NC resistance, provide compelling evidence that escape from NC activity is required before some transformed cells can grow as tumors in normal mice.

Animals↗
PubMed1985

Genetic markers of the antigen-specific T cell receptor locus.

The restriction enzyme Eco RI reveals DNA cleavage sites that serve to distinguish the gene locus believed to encode the beta subunit of the major histocompatibility complex (MHC)-restricted, antigen-specific receptor of the T cell in BALB/c mice from that of SJL/J mice. A monoclonal antibody, KJ16-133, also distinguishes BALB/c and SJL/J, because it recognizes an allotypic marker present on a cell-surface heterodimer believed to function as the MHC-restricted, antigen-specific T cell receptor. This study has shown that these two markers cosegregate in a set of BALB/c X SJL/J recombinant inbred (RI) mouse strains, permitting the conclusion that they are linked to within 3 centimorgans of each other, and to the kappa locus on chromosome 6. The tight linkage between these independently derived, totally different T cell markers substantially strengthens the argument that they characterize the MHC-restricted antigen-specific receptor of the effector T cell.

Alleles↗
PubMed1985

A monoclonal lambda 1-bearing anti-dextran antibody from a lambda-defective mouse strain.

A hybridoma from the lambda-defective mouse strain SJA has been established. It produces a lambda 1-bearing IgG2b, dextran B 1355-binding antibody. The DNA sequence of the VJ and C gene segment was in complete accordance with the published germ-line sequence. The rate of secretion and the steady state level of cytoplasmic RNA of this line was comparable to that of cell lines from normal mice. The idiotype was closely related to that of MOPC 104E indicating that the lambda 1 light chain is associated with the same VH region and in a similar fashion as in BALB/c mice. This antibody should be useful for further experiments on the lambda defect of SJL or SJA mice.

Animals↗
PubMed1985

A defined basal medium for study of in vitro T-cell responses.

A basal serum-free medium has been devised which supports short-term murine T-cell proliferative and functional assays in the absence of added lipids or serum albumin. Immune responses obtained with this medium are totally dependent on cell-cell interactions known to generate the lymphokines and monokines essential for replication and differentiation. Background activity is minimal, allowing better control of the specificity of response than is possible with serum-containing media. This medium is also suitable for the identification of added agents which modulate immune responses, and may facilitate the purification of secreted factors.

Animals↗
PubMed1985

Host genetic regulation of acute MHV-4 viral encephalomyelitis and acute experimental autoimmune encephalomyelitis in (BALB/cKe x SJL/J) recombinant-inbred mice.

In the present report we provide the strain distribution patterns of susceptibility to acute mouse hepatitis virus type-4 (MHV-4) encephalomyelitis, acute experimental allergic encephalomyelitis (EAE) and vasoactive amine sensitivity (VAAS) for 9 (CXJ) recombinant-inbred strains between BALB/cKe (C) and SJL/J(J) mice. We confirm that susceptibility to MHV-4 is not linked to the H-2 complex, and that all strains susceptible to acute EAE have both a responder H-2 haplotype (H-2s or H-2d) and induced (B. pertussis) VAAS. In addition, we provide evidence that susceptibility to acute EAE induction is controlled by an additional presently unmapped locus and that an EAE-like histopathological disease does not usually follow MHV-4 infection intracerebrally in animals susceptible to MHV-4, acute EAE and induced VAAS.

Animals↗
PubMed1985

Diversity in the immune system: "preconceived ideas" or ideas preconceived?

Two concepts of the evolution and regulation of expression of the combining site repertoire of the immune system, are compared. One view is based on the Associative Recognition Theory as formulated by the author and the other is based on the Idiotype Network Idea as conceived by Jerne. The two concepts are analyzed from the point of view of their logic, internal consistency and factual support.

Antibodies↗
PubMed1985

Effect of ticlopidine on neutrophil chemotaxis in rats.

The ex vivo effect of oral administration of ticlopidine on rat neutrophil chemotaxis was evaluated. Rats received either 3 oral doses (100 mg/kg body weight) of the drug, within a period of 48 h, via a gastric tube, or the drug was administered in drinking water for 14 days at a dosage of 75 mg/kg/day. Absorption of the drug was manifested by significant inhibition of adenosine diphosphate-(ADP-)induced platelet aggregation. No impairment of neutrophil chemotaxis toward zymosan-activated serum was observed in the ticlopidine-treated animals. These results indicate that concentrations of ticlopidine that significantly inhibit platelet function in rats are without effect on neutrophil chemotaxis toward zymosan-activated serum.

Adenosine Diphosphate↗
PubMed1985

Immunogenicity of a synthetic glucosyl-alpha(1,3)-glucosyl protein conjugate.

We compare antibody responses to nigerose [alpha(1,3) diglucoside] when it is presented as a hapten linked to keyhole limpet hemocyanin (N-KLH) or as a native constituent of dextran (B1355). In classic terms, N-KLH is thymus dependent (TD), whereas B1355 is thymus independent (TI). N-KLH only induced an in vitro antibody response in T-depleted splenic B cells when syngeneic, KLH-specific T helper cells (TH) were supplied. This need for H-2-restricted TH could not be supplanted by the addition of lymphokines (LK). In contrast, the response to B1355 only required the addition of LK. In vivo, N-KLH induced both kappa class and lambda class antibodies, unlike B1355, which induced a response that was restricted to the lambda class. N-KLH induced a substantial IgG response in vivo, with IgG1, IgG2a, and IgG2b subclasses increasing by two to three orders of magnitude over preimmunization levels. These isotypes were not found in the in vivo response to B1355. This is consistent with the TD and TI classifications of these immunogens. Antibodies induced by N-KLH were totally inhibited by the free alpha(1,3)-linked diglucosyl hapten, nigerose, as were those induced by B1355. In vitro, B1355 also induced a lambda predominant response in naive splenic B cells. However, prepriming with N-KLH resulted in a dramatic kappa class response to B1355. The data suggest that B cells can become responsive to TI antigens after TD activation.

Animals↗
PubMed1985

Analysis of immune surveillance of sequentially derived cell lines that differ in their tumorigenic potential.

The immune surveillance hypothesis suggests that cancer evolves as a multistage process. Further, it predicts that cells intermediate on the pathway to cancer are susceptible to host protective mechanisms, and only those variants that are able to escape the protective mechanisms are able to grow as tumors. We have isolated, as lineages, fibroblast lines that express phenotypes predicted by the surveillance hypothesis. The lineages were derived by treating nontransformed cells (N-cells) with chemical carcinogens and by isolating transformed variants in vitro. From the transformants that are tumorigenic in immune-depressed ATXFL mice but rejected by normal mice (I-cells), variants were selected in vivo that had escaped the rejection mechanism(s) and had grown as tumors in normal mice (C-cells). Thus lineages were established comprised of sequentially derived cell lines with the following phenotypes: nontransformed, transformed but susceptible to host protective mechanisms, transformed and resistant to host protective mechanisms (i.e., N----I----C). With the use of in vivo cross-protection experiments, two independently derived I-cell lines were shown to express non-cross-reactive antigens that are not expressed by the parental nontransformed N-cells (i.e., transformation-associated antigens). The transformation-associated antigens are expressed at an equivalent level on the cells that are susceptible to rejection (i.e., I-lines) and those that have escaped rejection (i.e., C-lines). In addition, although the transformation-associated antigens expressed by I-cells induce an effective immune response capable of rejecting both the I-line and C-line, the expression of these antigens on C-cells does not induce an effective immune response. The role of host defense mechanisms in the rejection of these chemically transformed I-cells and the possible mechanisms by which C-cells escape rejection are discussed.

Animals↗
PubMed1985

Non-H-2-linked control of in vivo growth of SJL/J-derived reticulum cell sarcoma in recombinant inbred strains between BALB/cKe and SJL/J mice.

This report investigated the growth of reticulum cell sarcoma (RCS) in several congenic and recombinant inbred strains between BALB/cKe female (H-2d) and SJL/J male (H-2s) mice. SJA20 mice congenic with SJL/J except at the Igh locus supported RCS growth. Recombinant mice of the H-2d haplotype did not support RCS growth. However, recombinant inbred mice of the H-2s haplotype varied in their susceptibility to permit RCS growth in vivo. These results supported the role of non-H-2 gene(s) controlling the growth of RCS. Since the recombinant strains of mice exhibited different immunologic characteristics and since RCS tumor growth depended on the ability of the mice to develop a strong antitumor proliferative response, the findings reported here suggested that non-H-2 genes control the magnitude of the syngeneic proliferative response and consequently regulate RCS growth in vivo.

Animals↗
PubMed1983

Evidence that cytotoxic T cells and natural cytotoxic cells use different lytic mechanisms to lyse the same targets.

There is evidence that natural cytotoxic (NC) cells are in the T cell lineage. To lyse targets, cytotoxic T cells (TK) must recognize any of the myriad antigens plus syngeneic major histocompatibility complex (MHC) determinants. In spite of the evidence which indicates TK and NC are in the same lineage, NC cells can recognize few determinants (perhaps only one) and do not require recognition of MHC determinants. In addition to differences in the requirement for target recognition, in this report we show that TK cells and NC cells also use different lytic mechanisms to lyse the same targets. NC effectors initiate a lytic mechanism in NC-sensitive and NC-resistant targets. This lytic mechanism requires approximately 4 h before target lysis is apparent in NC-sensitive targets; it is inactivated by a protein synthesis-dependent counterlytic mechanism in NC-resistant targets. In contrast the TK lytic mechanism causes a rapid release of 51Cr from both NC-sensitive and NC-resistant targets and is not inhibited by the NC counterlytic mechanism present in NC-resistant cells. These findings lead to the conclusion that the mechanism used by NC cells to lyse targets is fundamentally different from that used by TK cells.

Animals↗
PubMed1983

The T-cell receptor mediating restrictive recognition of antigen.

Four facts characterize restrictive recognition of antigen. First, in large measure, allele-specific determinants on R are recognized when R is functioning either as a restricting element (RL) or as an allo-target (or even xeno-target) (RF). Second, there is a high frequency of virgin antigen-responsive t cells with alloreactivity, i.e. anti-RF. Third, there is a strict relationship between the class of effector function and the class of RL recognized (restrictive recognition of antigen, XF) but a relaxed relationship between class of effector function and class of RF recognized (alloreactivity). Fourth, the effector T cell functions anti-RL-dependently when XF is the target (restrictive recognition of antigen) and anti-RL-independently when RF is the target (alloreactivity). From these facts are derived the following conclusions. The T cell uses a dual recognitive, single receptor (Model I, Figure 1). A single germ-line VT locus specifying anti-allele-specific recognition of species R encodes both the anti-R and the anti-X combining sites. A "learning" process (occurring in the thymus) is required to establish the restriction specificity (anti-RL) as well as the effector function/class of RL relationship. The repertoire is derived by somatic mutation of all germ-line VT genes specifying anti-RF (Model IA, Table 3 and Figure 9). Given Model IA (Table 3 and Figure 9), we can account further for the existence of an extensive polymorphism of R and minimal polygeneism, for the high frequency of crossreactivity between anti-XF and RF, and for the physiology and genetics of cell-cell communication in immune responsiveness.

Animals↗