Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary anti-phosphorylcholine (PC) response in BALB/c, C57BL/6, and congenic and recombinant inbred strains of these parental types has been examined in the splenic focus system. The frequencies of PC-specific precursors were shown to vary among these strains from 2 to 20 precursors per 10(6) splenic B cells. The distribution of these frequencies suggests that elements closely linked to or within the major histocompatibility complex may play a role in the determination of this parameter, although additional experiments are necessary to adequately assess this possibility. Moreover, all strains tested, regardless of immunoglobulin allotype, expressed monoclonal antibodies indistinguishable from the TEPC 15 myeloma protein (T15) clonotype. Further, the frequency of this clonotype in a given strain did not appear related to allotype, since both high and low T15 frequencies were found among strains of either the BALB/c (a(1)) or C57BL/6 (a(2)) allotype. The examination of normal serum for the T15 idiotype, however, revealed that only mice of the BALB/c allotype (a(1)) expressed the T15 idiotype in detectable quantities. After immunization with Diplococcus pneumoniae, sera from mice of the a(1) allotype consistently contained large quantities of the T15 idiotype, whereas sera from mice of the a(2) allotype exhibited various degrees of cross-reactivity with anti-T15 antibody. These results suggest that: (a) the allotype of an individual, although closely related to serum levels of an idiotype, is unrelated to the proportion of the precursor population which expresses that idiotype and; (b) the serum expression of a given idiotype may reflect regulatory processes, which act either during or before antigenic stimulation, rather than the actual clonotype representation in the repertoire. These findings indicate that distinctions must be made between the expression of idiotypic determinants within precursor B-cell populations and elements which regulate the subsequent appearance of those idiotypes in serum antibodies.
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PMID:Differential expression of an equivalent clonotype among BALB/c and C57BL/6 mice. 7 30

During each transplantation passage of a line of mouse myeloma tumor MOPC-315 through syngeneic (BALB/c) hosts, the tumor cells lose reactivity with cytotoxic thymus-derived lymphocytes directed against products of the BALB/c major histocompatibility complex (H-2d) and regain reactivity on transfer to fresh hosts. In contrast to this cyclical change, the tumor cells remain uniformly reactive with anti-H-2d alloantisera throughout the transplantation cycle.
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PMID:Periodic loss of reactivity of a myeloma tumor with cytotoxic thymus-derived lymphocytes. 7 47

To investigate the antigenic relationship between the macrophage and lymphocyte Fc receptors (FcR), a monoclonal antibody capable of blocking mouse macrophage Fc receptors was selected. Hybrids were formed by fusing the P3U1 mouse myeloma and spleen cells from a rat immunized with the mouse macrophage-like cell lines J774 and P388D1. The Fab fragment of the monoclonal IgG secreted by clone 2.4G2, inhibited the trypsin-resistant Fc receptor II (FcRII), which is specific for immune aggregates of mouse IgG1 and IgG2b, but had no inhibitory effect on the trypsin-sensitive Fc receptor I (FcRI), which binds monomeric IgG2a and erythrocytes coated with IgG2a. Thus, the monoclonal 2.4G2 IgG appeared to be specific for macrophage FcRII. Further evidence that the 2.4G2 IgG was directed against FcRII came from binding studies of the monoclonal antibody to J774 cells and a series of independently isolated variants which do not express FcRII. These variants of J774 bound 5% as much of the monoclonal antibody as the parent line, which bound 600,000 molecules of 2.4G2 IgG per cell. The antigenic relatedness of mouse lymphocyte FcR to mouse macrophage FcRII was demonstrated by the binding of 2.4G2 IgG to FcR-bearing lymphoid cell lines and the inhibition of the lymphocyte FcR by the monoclonal antibody. Preincubation of spleen cells and peritioneal cells with 2.3G2 IgG likewise inhibited rosette formation with ox erythrocytes coated with rabbit IgG. The ability of the hybridoma IgG to inhibit mouse FcRII was independent of the major histocompatibility complex. The 2.4G2 IgG antigenic determinant was not present on rat, guinea pig, rabbit, or human FcR-bearing cells.
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PMID:Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. 9 Jan 8

Spleen cells from a LEW.AVN rat immunized with cells from an MNR rat were fused with mouse myeloma cells to produce hybrid cell lines. One of these hybridomas produced a monoclonal antibody that was cytotoxic for bone marrow-derived (B) but not thymus-derived (T) cells. The antigen defined by this antibody is determined by a gene linked to the major histocompatibility complex (MHC). The antigen is also present on B cells of most mouse strains and is determined by an MHC-linked gene in this species as well. In both rats and mice, the gene determining the antigen maps within the immune response region of the MHC. All human B-cell lines, but not T-cell lines, and B but not T cells of all human donors tested so far are also positive for this antigen. Among human-mouse somatic cell lines that have lost various human chromosomes, this B-cell antigen is present on all lines that are positive for HLA antigen but is absent from all lines that have lost HLA.
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PMID:Monoclonal antibody directed to a B-cell antigen present in rats, mice, and humans. 31 63

Two mutant cell lines derived from the MPC-11 mouse myeloma synthesize immunoglobulin with abnormal heavy chains and normal light chains. The defective heavy chains have molecular weights of 38,000-42,000 (M3.11) and 50,000 daltons (ICR 11.19) as compared to 55,000 daltons of the wild-type. The glycosylation of the defective heavy chains demostrated several unusual features: first, 30-50% of the M3.11 heavy chain contained no carbonydrate, while 100% of the wildtype and ICR 11.19 heavy chains were glycosylated; second, the glycopeptides of the M3.11 heavy chains revealed an altered gel filtration pattern when compared with the wild-type; and third, digestion with an endoglycosidase indicated that the heterogeneity of the wild-type and M3.11 glycopeptides involved structural changes in the core region of the oligosaccharide. Examination of two other glycoproteins (the major histocompatibility complex antigens) in these cell lines showed that in M3.11, the H-2D but not the H-2K product was abnormally glycosylated and contained a smaller glycopeptide. However, in a subclone of M3.11 that had lost the ability to produce immunoglobulin heavy chains, the H-2D glycopeptide had returned to wild-type size. We concluded from these studies that the defective M3.11 immunoglobulin heavy chain interfered both with its own glycosylation and the glycosylation of another protein, H-2D.
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PMID:Abnormalities in the glycosylation of immunoglobulin heavy chain and an h-2 transplantation antigen in a mouse myeloma mutant. 40 5

The genetics of hybrid susceptibility of parental myeloma transplants in histocompatible F1 hybrids was investigated. Various inbred mouse strains and their descendant congenic lines were crossed with BALB/C mice to produce appropriate F1 hybrids. Genetic inferences were drawn from the comparison of the frequencies of tumor graft takes among congenic combinations. Hybrids containing the C57BL/10 genetic background were less susceptible to myeloma transplants than were hybrids of other genotypes. Both H-2-associated and non-H-2-associated genetic factors played significant roles in determining host susceptibility to the transplants. The D end of the major histocompatibility complex did not play a predominant role in determining hybrid susceptibility in C57BL-derived F1 hybrids.
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PMID:Genetics of F1 hybrid susceptibility to myeloma grafts. 44 94

A monoclonal antibody, B20.1, was generated by fusing spleen cells from a Lou rat immunized with a soluble alpha/beta T cell receptor (TcR; V alpha 2/V beta 2) to mouse myeloma cells. Analysis of a panel of V alpha 2 mRNA-expressing T cell lines, hybridomas and transfectants revealed that the B20.1 antibody was specific for murine TcR V alpha 2 chains. The V alpha 2+ T cell population was examined in various inbred strains by two-color immunofluorescence using B20.1 and CD4- and CD8-specific antibodies with the following results: (a) the B20.1 antibody detected most members of the TcR V alpha 2 subfamily in the four TcR V alpha haplotypes tested; (b) in most strains examined, TcR V alpha 2 expression was biased to the CD4 subset (7.4%-17.4% V alpha 2+ T cells) as compared to the CD8 compartment (3.8%-13.3%); (c) TcR V alpha 2 expression was not influenced by Mls gene products and (d) increased positive selection of V alpha 2+ CD8+ T cells by H-2k major histocompatibility complex molecules occurred in all murine strains tested of the TcR V alpha a, but not in those bearing the TcR V alpha b haplotype.
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PMID:Preferential positive selection of V alpha 2+ CD8+ T cells in mouse strains expressing both H-2k and T cell receptor V alpha a haplotypes: determination with a V alpha 2-specific monoclonal antibody. 131 Dec 60

The T-cell receptor is necessary and sufficient for recognition of peptides presented by major histocompatibility complex molecules. Other adhesion molecules, like CD4 or CD8, play an auxiliary role in antigen recognition by T cells. Here we analyse T-cell receptor (TCR) binding using a soluble rather than a cell-bound receptor molecule. A TCR-immunoglobulin chimaera is constructed with the variable and the first constant regions of both the TCR alpha- and beta-chains linked to the immunoglobulin light-chain constant regions. This soluble TCR is expressed, assembled and secreted as an alpha beta heterodimer by a myeloma cell line transfected with the recombinant genes. Furthermore, the soluble TCR is biologically active: it specifically inhibits antigen-dependent activation of the relevant T-cell clones and thus discriminates between proper and irrelevant peptides presented by major histocompatibility complex molecules.
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PMID:Specific low-affinity recognition of major histocompatibility complex plus peptide by soluble T-cell receptor. 157 13

Changes in the antigenicity of major histocompatibility complex (MHC) class I molecules resulting from the association of bovine beta 2-microglobulin (beta 2-m) with mouse class I heavy chains were investigated. Mice (H-2b) were immunized with syngeneic Concanavalin A (Con A) blasts induced in the presence of fetal calf serum (FCS) in conditions allowing exchange between mouse and bovine beta 2-microglobulin (beta 2-m). Spleen cells from hyperimmunized mice were fused with myeloma cells and two monoclonal antibodies which required for their reactivity the presence of FCS have been further studied. One of them (CAB 297) recognized a determinant of bovine beta 2-m which is present on free molecules in solution as well as when they are associated with either mouse or bovine class I heavy chains. In contrast, the second monoclonal antibody (CBB 70) did not react with free bovine beta 2-m molecules, nor with beta 2-m associated with bovine class I heavy chains. It did react with cells of some H-2 haplotypes (b, f, p and r) but only when their class I heavy chains are associated with bovine or with human beta 2-m. Therefore, expression of the CBB 70 defined antigenic determinant requires both xenogeneic beta 2-m and class I heavy chain of a given H-2 molecule. In order to precisely localize the antigenic determinant defined by this monoclonal antibody and therefore the region altered by the association of class I heavy chain with xenogeneic beta 2-m, we made use of exon shuffled class I molecules. The results indicate that changes induced by the association of bovine beta 2-m with H-2 class I heavy chain affect the conformation of the alpha 2 domain. These studies illustrate that MHC class I molecules exhibit a considerable conformational flexibility which could influence their ability to bind and present various peptides to the T-cell receptor.
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PMID:Localization of the conformational alteration of MHC molecules induced by the association of mouse class I heavy chain with a xenogeneic beta 2-microglobulin. 137 66

We have sequenced the T cell receptor (TcR) V alpha and V beta genes of seven independent BALB/c CD4+ T cell clones specific for the immunoglobulin lambda 2 light chain produced by the MOPC 315 myeloma (lambda 2(315)). All the clones recognize a peptide of residues 91-101 of lambda 2(315) and are restricted by the major histocompatibility complex (MHC) molecule I-E(d). The results indicate that in BALB/c mice, this anti-idiotypic response uses a very limited number of TcR. The four clones which cross-react between Phe94 and Tyr94 peptide analogues use very similar receptors (V alpha 3, J alpha 1, V beta 6, J beta 1.1). The V alpha 3 gene used by all of these clones is identical and has not been previously described. Although the four clones differ in nucleotide sequence in the V/J borders, two had identical receptors at the amino acid level. One of the cross-reactive clones exhibits a heteroclitic response to the Tyr94 peptide variant resulting from a single amino acid exchange in the V/J junction of the alpha chain. The three remaining clones which recognize only the Phe94 and not the Tyr94 peptide have somewhat more diverse TcR, however, two of these three clones use V beta 6. One of these non-crossreacting clones is alloreactive, the specificity of which can be attributed to differences in the N-D-J sequences. Taken together these data indicate that this T cell response to an immunoglobulin idiotope is very restricted in terms of the TcR used. These data in conjunction with recently published results indicate that, although there can be strong preference for individual V alpha or V beta gene segments, certain V alpha/V beta combinations are preferentially selected for interacting with a given peptide/MHC combination, and that the CDR3-related regions are crucial for antigen fine specificity and alloreactivity.
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PMID:Restricted alpha/beta receptor gene usage of idiotype-specific major histocompatibility complex-restricted T cells: selection for CDR3-related sequences. 137 89


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