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R Riblet

Publications and source records attributed to R Riblet.

At least 55 records · Page 3Linked to original sources

Genes for the mouse T cell alloantigens Tpre, Tthy, Tind, and Tsu are closely linked near Igh on chromosome 12.

Genes encoding the T cell alloantigens Tpre, Tthy, Tind, and Tsu have been mapped to a short segment of chromosome 12 using Igh recombinant strains of mice. These loci are located in a tightly linked cluster between the immunoglobulin heavy chain constant region gene cluster, Igh-C, and the serum prealbumin locus Pre-1, in this manner: centromere--Igh-C--(Tthy, Tind)-Tsu-Tpre--Pre-1.

Animals↗

The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes.

Seven families of Igh-V genes have been defined by Southern blot analysis of genomic DNA from eighteen inbred strains of mice. Each of twenty-four cloned Vh genes hybridized to one of seven nonoverlapping sets of Eco RI restriction fragments. These families contain from 2 to approximately 40 hybridizing fragments. From these data we estimate that the mouse Igh-V locus consists of one hundred Vh genes. Genes within a Vh family share greater than 80% sequence homology while the sequence homology between families is generally less than 70%. There is extensive restriction fragment length polymorphism among the strains analyzed allowing the assignment of complete (Igh-V + Igh-C) Igh haplotypes for eighteen inbred mouse strains.

Animals↗

Identification and mapping of Lm-1, an Igh-linked locus for a murine alloantigen.

Analyzing Igh congenic, Igh recombinant, and recombinant inbred mouse strains with a cytotoxic T-cell assay, we have identified and mapped an Igh-linked locus (Lm-1) that codes for a cell-surface alloantigen (Lm-1). Lm-1 maps 5 units telomeric to Pre-1 and is genetically distinct from previously described Igh-linked loci. The importance of Lm-1 and its possible relationship to other Igh-linked alloantigens is discussed.

Animals↗

H-40, an antigen controlled by an Igh-linked gene and recognized by cytotoxic T lymphocytes. II. Recognition of H-40 as a tumor antigen in leukemic animals.

C.B-20 (Ighb) but not (C.B-20 X BALB/c)F1 mice reject BCL1, a sIg+ tumor that spontaneously arose in an Igh congenic BALB/c (Igha) mouse. C.B-20 immune T cells from mice immunized with either BCL1 or BALB/c splenocytes adoptively transfer tumor protection to sublethally irradiated C.B-20 but not BALB/c or (BALB/c X C.B-20)F1 mice. These data suggest that BALB/c and BCL1 share an antigen, which if present in the host prevents the immune cells from eradicating the tumor. The antigen is controlled by H-40, a gene that maps to the C end of the Igh complex, telomeric to Tsu and in the region of Pre-1. The ability of H-40 to act as a tumor antigen for other BALB/c tumors inoculated into C.B-20 hosts was investigated. H-40 did not elicit rejection of P1798 (T lymphoma), Meth A (fibrosarcoma), or MOPC-315 (alpha, lambda myeloma) tumor cells. C.B-20 mice that previously rejected BCL1, however, showed partial resistance to a low challenge dose of the MOPC-104E (mu, lambda myeloma) tumor. These data suggest that H-40 has a differential degree of expression on BALB/c tumor cells. The ability of the adoptively transferred cells to confer protection against BCL1 is abrogated by pretreatment of the cells with anti-Lyt-1 or anti-Lyt-2 antibodies. However, an admixture of anti-Lyt-1- and anti-Lyt-2-treated cells provided protection. These data, together with the results detected by cytotoxic T lymphocyte (CTL) activity in vitro, indicate that H-40 can serve as a target antigen for tumor rejection by CTL in allogeneic hosts. The implications of the results for allogeneic bone marrow transplantation into leukemic individuals who benefit from a graft vs leukemia effect are discussed.

Animals↗

c-myc Gene rearrangements involving gamma immunoglobulin heavy chain gene switch regions in murine plasmacytomas.

In murine plasmacytomas, the c-myc gene has frequently been found to undergo rearrangement by virtue of a T(12;15) chromosome translocation. The immunoglobulin heavy chain gene switch region (S alpha) constitutes the target for most of these recombinations particularly in IgA producing plasmacytomas. We sought to identify non-S alpha myc target sites in several IgG producing tumors. The c-myc target in MPC-11 (a BALB/c IgG2b producing plasmacytoma) has been cloned, localized to the Igh-C locus and identified as the gamma 2a heavy chain gene switch region (S gamma 2a). Furthermore, by Southern blot hybridization, we have determined that the S gamma 2b region is the c-myc target in two NZB IgG2b producing plasmacytomas. The potential relation between Ig class expressed and c-myc translocation target is discussed.

Animals↗

T suppressor cells activated by anti-Tsud serum are Igh-V-restricted.

T suppressor (Ts) cells can be activated by alloantiserum directed against Tsud, a cell surface marker associated with the Ts cell receptor for antigen. These cells are restricted in their ability to transfer suppression in allotype-congenic mice. Transfer of suppression requires matching of donor recipient mice at Igh-V loci, but recipient mice need not share the Tsud allele nor the same allotype as the activated Ts cells. Genes linked to the kappa light chain locus apparently do not affect this transfer.

Animals↗

The genetic basis of antibody production: the dominant anti-arsonate idiotype response of the strain A mouse.

Immunization of the A strain of mice with the hapten p-azophenylarsonate (Ars) results in an immune response in which approximately 50% of the anti-Ars antibodies share cross-reactive idiotypic determinants (IdCR). A gene or genes linked to the heavy chain constant region locus is required for the production of this idiotype. The expressed VH gene from a hybridoma cell line which expresses the IdCR has been cloned. DNA hybridization studies utilizing the VH gene have revealed that there are many related genes in both idiotype-producing and idiotype-nonproducing strains of mice. However, under stringent hybridization conditions, only a single band of 6.4 kb is present in Eco R1-digested A strain DNA. Strains of mice which are phenotypically idiotype-negative either lack this band completely or possess a much weaker one at this position. Utilizing DNA from Igh recombinant strains of mice, it has been shown that the VH locus controlling idiotype expression contains the structural gene information for the idiotype-positive heavy chains. It has also been shown that DNA at this locus appears to be sufficient for the production of the cross-reactive idiotype. Utilizing a DNA probe derived from regions flanking the structural gene has confirmed the relatedness of V genes in a variety of mouse strains and revealed a significant degree of polymorphism at the Igh locus.

Animals↗

The T suppressor cell alloantigen Tsud maps near immunoglobulin allotype genes and may be an heavy chain constant-region marker on a T cell receptor.

The mouse T cell alloantigen, Tsud, is expressed on a minority of mature, Lyt-2+ cells, and its expression is controlled by a gene linked to the immunoglobulin heavy chain gene cluster, Igh. Tsud can be assayed by immunofluorescence staining with an antiserum made in BALB/c mice against C.AL-20 concanavalin A blasts. This antiserum can also be used to induced T suppressor cells in mice expressing Tsu(d). Both of these assays were used to type several panels of recombinant inbred strains and Igh recombinant strains to accurately map the Tsu(d) locus. The Tsu(d) gene is located very near the heavy chain constant-region genes, Igh-C, on the side toward the prealbumin gene, Pre-1. Tsu(d) is not among the heavy chain variable-region genes, Igh-V, and thus is not a variable-region framework allotype, subgroup determinant, or idiotype. The map position suggest that the Tsu(d) antigen is a constant region allotypic determinant on the as yet uncharacterized T cell receptor.

Animals↗

Maternally transmitted target antigen for unrestricted killing by NZB T lymphocytes.

A new target antigen for unrestricted killing was defined by NZB T lymphocytes which were immunized and restimulated with H-2-identical BALB/c spleen cells. These effector cells killed nearly all target cells tested, irrespective of their H-2 type, but did not kill NZB target cells. The response was shown to have three major components: unrestricted killing specific for Qed-1b, H-2d-restricted killing specific for minor histocompatibility antigens, and unrestricted killing specific for a new antigen, Mta. Mta is present on normal and mitogen-stimulated T and B lymphocytes and on several tumor lines. It was found on cells from 26 mouse strains tested, including two substrains of NZB, representing 9 different H-2 types and 14 different non-H-2 backgrounds. Analysis of the NX8 recombinant inbred lines (derived from Mta-NZB/Icr and Mta+C58/J parents) suggested that Mta is maternally transmitted. This was confirmed by typing of reciprocal F1 hybrids and backcrosses between positive and negative strains: Mta+ females bear Mta+ offspring and Mta- females Mta- offspring, irrespective of the phenotype of the males.

Animals↗

Antibody gene linkage studies in (NZB X C58) recombinant-inbred lines.

A set of recombinant inbred mouse strains has been constructed from the cross of NZB by C58. These strains provide new tools for the analysis of antibody heavy and light chain genes and NZB autoimmunity. Typing of heavy chain genes confirmed the allotype linkage of the dextran response locus Igh-Dex. One strain has fixed a recombinant chromosome carrying NZB allotype genes and the Dex+ variable region gene from C58. Two kappa-light chain variable region genes, Igk-Pc and Igk-Ef1, co-segregated with the Lyt-2 lymphocyte alloantigen locus. This confirms the tight linkage of these loci and decreases the maximum estimate of the recombination frequency between them to 1.7%.

Animals↗

Myeloma proteins from NZB and BALB/c mice: structural and functional differences.

Structural and functional analyses of myeloma immunoglobulins from inbred BALB/c mice and humans have provided important insights into the structure of the antibody molecule and the expression and evolution of antibody genes. One important question concerning these analyses is whether the myeloma process selects, in a nonrandom manner, the lymphocytes to be transformed. The availability of myeloma tumors in a second inbred strain of mouse, NZB, permits us to approach this question. In this respect. the NH2-terminal amino acid sequences of 27 kappa light chains as well as data relating to the antigen-binding properties and immunoglobulin class distribution of NZB myeloma proteins are presented and compared with similar data from the BALB/c mouse. These studies suggest that the myeloma proteins from the BALB/c and NZB mice constitute two populations of immunoglobulins with distinct functional and structural properties. The implication of this observation are discussed.

Amino Acid Sequence↗

Comparisons of myeloma proteins from NZB and BALB/c mice: structural and functional differences of heavy chains.

The N-terminal sequences from heavy variable regions of 47 myeloma proteins of the NZB mouse have been analyzed. Sixteen of these VH regions have unblocked alpha amino groups and have been analyzed over their N-terminal 20 residues by automatic sequence analysis. These sequence data along with the antigen-binding profiles and immunoglobulin class distribution are compared with comparable data from BALB/c myeloma proteins. These comparisons suggest that the NZB and BALB/c populations of myeloma proteins are distinct from one another. The genetic implications of this conclusion are discussed.

Amino Acid Sequence↗

Plasmacytomas of the NZB mouse.

Plasmacytomas were readily induced in NZB mice by three i.p. inoculations with pristane (2, 6, 10, 14-tetramethylpentadecane). In comparison with comparable induction regimens in BALB/c mice a) the latent period for plasmacytoma development was significantly longer in NZB's; b) the frequency of IgA paraproteins produced by NZB tumors was much reduced and that of IgG (IgG1, IgG2a, IgG2b, IgG3Y was significantly increased; and c) the frequency of carbohydrate-binding paraproteins was 10-fold lower. There was a high frequency of primary ascites containing more than one paraprotein, but none of 25 such tumors produced more than one immunoglobulin class on serial transplantation.

Animals↗

The response of recombinant inbred strains of mice to bacterial lipopolysaccharides.

Fourteen recombinant inbred strains of mice have been produced by the inbreeding of the F2 generation of a cross between C57BL/6J and C3H/HeJ progenitor mice. The responses of these BXH strains to bacterial lipopolysaccharides (LPS) have been characterized. Four BXH strains are high LPS responders and nine strains are low LPS responders. One BXH strain shows intermediate responsiveness which may reflect residual heterozygosity. F1 hybrid mice from low x high responder strains were intermediate in their response to LPS suggesting additive genetic control. The LPS responses in backcross mice from the F1 x low LPS responders showed segregation consistent with LPS responsiveness being determined by a single gene. In 13/14 BXH strains, there was concordant inheritance of LPS responsiveness and the major urinary protein locus Mup-1b. The association of the expression of the Mup-1 alleles with LPS responsiveness in the BXH strains suggests that the defective LPS response gene in C3H/HeJ mice is located on chromosome 4.

Animals↗

Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS.

The mechanism was investigated underlying the activity of bacterial lipopolysaccharide (LPS) as an adjuvant of antibody formation as assessed by its capacity to modulate the induction of tolerance in mice to the antigen human Ig G (HGG) into a state of immunity to HGG. The adjuvant activity of LPS was found to be closely correlated with its ability to function as a B-cell mitogen. This correlation was revealed by an analysis of the genetic control of the mitogenic and adjuvant properties of LPS utilizing the refractory state inherent in the C3H/HeJ mouse strain to these activities of LPS. Thus, mice that were the progeny of a backcross between the nonresponder C3H/JeJ parent and the responder (C3H/HeJ X CWB) F1 hybrid were individually typed for responsiveness to LPS, as an adjuvant and as a B-cell mitogen. It was found that LPS interfered with tolerance induction to HGG in vivo only in those backcross progeny whose spleen cells were also capable of responding mitogenically to LPS in vitro, demonstrating that the adjuvant and B-cell mitogenic properties of LPS are genetically linked. In contrast, these properties were observed to segregate independently from either H-2 or heavy chain allotype loci, and were not sex linked. These results are compatible with the concepts that, in this system, (a) the cellular site of action of LPS as an adjuvant is confined to B cells, and (b) the subcellular mode of action of LPS as an adjuvant may involve the delivery of a "signal" to B cells which is a stimulus for mitogenesis.

Adjuvants, Immunologic↗