Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A low-molecular-weight protein, beta2-mu, isolated from urine and other biological fluids was shown to have an amino acid sequence related to constant regions of the immunoglobulin heavy chain--to CH3 comain in particular. Several homologues of this protein were also isolated and partially sequenced. The protein was shown to be localized in the membranes of nucleated cells and found to be associated with HL-A antigens. Its biological and/or immunological function is still unknown; however, it binds to complement and is cytophilic to guinea pig macrophages as well as to other cells. Antibodies to beta1-mu can act as mitogens and can blcok stimulation in MLCs but not recognition by "killer" lymphocytes.
Contemp Top Mol Immunol 1975
PMID:beta2-Microglobulins. 5 15

In about 80% of Burkitt's lymphoma cases, the tumour cell harbours a reciprocal chromosomal translocation which invariably transposes the coding exons 2 and 3 of c-myc from chromosome 8 to the immunoglobulin heavy chain locus on chromosome 14. Those t(8;14) translocations which disrupt chromosome 8 within or close to the c-myc gene are well documented. In this study we have focussed on t(8;14) translocations with the chromosomal breakpoint far upstream of c-myc. We analyzed the breakpoint position in 44 BL cell lines with t(8;14) translocations of different geographical origin and identified 9 cell lines with the breakpoint more than 14 kb upstream of c-myc. In these cell lines the positions of the translocation junctions on the derivative chromosomes 8q- and 14q+ were mapped by pulsed field gel electrophoresis and multicolour fluorescence in situ hybridization. The breakpoints occur at distances between 55 and more than 340 kb upstream of c-myc with no preferential site on chromosome 8. On chromosome 14, however, the translocation breakpoints are clustered in a narrow region 5' of the intron enhancer of the immunoglobulin heavy chain gene. In 7 of 9 cases, the enhancer is fused to the c-myc bearing sequences of chromosome 8. In two cases, the translocation has occurred in switch mu and downstream of C mu, respectively. The impact of these results with respect to the hypothesis, that cis-regulatory sequences from the immunoglobulin heavy chain locus can deregulate c-myc expression in a manner sufficient for tumour formation, is discussed.
Hum Mol Genet 1992 Nov
PMID:Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14) translocation separate c-myc and the IgH locus up to several hundred kb. 130 Nov 71

The translocation t(14;18)(q32;q21) occurs in 70% of follicular lymphomas and places the BCL2 proto-oncogene, normally located at 18q21, under the control of the immunoglobulin heavy chain (IgH) gene at 14q32. Its detection by the polymerase chain reaction (PCR), made possible by the close clustering of most of the BCL2 breakpoints in the major breakpoint region (MBR) of the gene, has numerous clinical applications. Since the PCR covers shorter lengths of DNA than Southern blotting, PCR-based tests may be more susceptible to microheterogeneity in breakpoint location. There have been no published studies of the impact of breakpoint microheterogeneity on the detection rate of this translocation by PCR. We studied 30 follicular lymphomas with the t(14;18), in which a BCL2 MBR rearrangement had previously been demonstrated and mapped by conventional Southern blotting, by PCR with the commonly used IgH and BCL2 MBR primers. Twenty-five cases (83%) had a junction fragment demonstrable by PCR. All three cases in which the MBR rearrangement mapped outside of the 4.3-kb HindIII fragment containing the MBR, as determined by Southern blotting, were negative by PCR. In addition, two cases with rearrangements within the HindIII fragment were also negative. All negative results were repeated at least once and were confirmed to be true negatives by actin PCR. Our results suggest that negative PCR results in this setting are attributable to small variations in BCL2 MBR breakpoint location and cannot be interpreted without the corresponding conventional Southern blotting data. With this caveat in mind, PCR analysis for the t(14;18) remains an extremely useful technique, especially in the follow-up and monitoring for minimal residual disease in previously characterized cases of follicular lymphoma.
Diagn Mol Pathol 1992 Mar
PMID:Detection of rearrangements of the BCL2 major breakpoint region in follicular lymphomas. Correlation of polymerase chain reaction results with Southern blot analysis. 134 52

Erythrocytes (E) play a central role in handling circulating immune complexes (IC) in primates. E capture IC via complement receptors, type 1 (CR1) which can bind to C3b and C4b ligand sites generated on IC during activation of the complement cascade. The present study was designed to explore how the immunochemical properties of IC affected their interactions with human E. Model IC were constructed by combining murine monoclonal anti-dinitrophenyl (DNP) antibodies with DNP-bovine serum albumin. A panel of 10 independently-derived monoclonal IgG1, IgG2a, IgG2b, IgG3, IgM and IgA antibodies were used to construct IC and their interactions with human E were examined in vitro. The data reveal that IC constructed with the different monoclonal antibodies differed with respect to their rate of binding to E, the peak magnitude of IC binding to E, and the rate and extent of IC release from E. IC containing IgG1 antibodies (IgG1 IC), IgG2a IC, IgG2b IC, and IgA IC all bound rapidly to E, whereas IgG3 IC and IgM IC were bound relatively slowly to E. The peak magnitude of IC binding to E correlated directly with their binding rate. There was an inverse correlation between the antigen/antibody ratio of the IC and the magnitude of IC binding to E. The rate of release of the various types of IC from E also differed. IgG2a IC and IgG2b IC displayed the most rapid maximum release rates while IgG3 IC had the slowest peak release rate. IgM IC and IgA IC were also released relatively slowly from E. IgG1 IC had an intermediate release rate. There was no direct correlation between the maximum release rate and either the maximum binding rate or the peak magnitude of IC binding to E. While there were some clonotypic differences in binding and release rates between IC made with different IgG2a, IgG3 and IgM antibodies, antibody isotype appears to be of fundamental importance with respect to both the binding of IC to E and the release of IC from E. These data indicate that the immunochemical properties of IC can profoundly affect their interactions with human E and that the panel of IC constructed with monoclonal antibodies can serve as a useful model to explore these interactions.
Mol Immunol
PMID:Isotypic and clonal variations in the interactions between model monoclonal immune complexes and the human erythrocyte CR1 receptor. 138 41

We report the construction and the expression in Escherichia coli of three different fusion genes encoding the extended human IgG3 hinge region (Hi) fused in-phase to the C-terminal end of bacterial TEM1 beta-lactamase (Bla). In the first fusion gene blahi, TEM1 beta-lactamase (Bla). In the first fusion gene blahi, the hinge sequence was directly coupled to the 3' end of the beta-lactamase gene, whereas in the two other constructs, blal1hi and blal2hi, a linker encoding 14 and 10 amino acids, respectively, was inserted between the two subunits. After expression (24 h, 20 degrees C) under control of the constitutive kanamycin phosphoribosyl transferase promoter, the fusion proteins, BlaHi, BlaL1Hi and BlaL2Hi, respectively, were almost exclusively detected in the periplasmic fraction, and they conferred carbenicillin-resistance to the cells. These results indicate that beta-lactamase can efficiently direct the export of proteins fused to its C-terminus, and moreover, at least some of the exported fusion proteins must carry the beta-lactamase moiety in a properly folded form. Analysis of their assembly, however, revealed that only a minor fraction was recovered as the expected F(ab')2-like dimer. The presence in the periplasm of 'oxidized' monomers (with intrachain disulphide bonds) as well as of several high-molecular-mass proteins, probably resulting from the association between monomers and other cysteine-rich proteins, strongly suggests that the conditions in the bacterial periplasm are insufficient to allow proper assembly of multimeric proteins with several interchain disulphide bonds.
Mol Microbiol 1992 Aug
PMID:Disulphide bridge formation in the periplasm of Escherichia coli: beta-lactamase:: human IgG3 hinge fusions as a model system. 140 60

The anti-TAG72 Fv molecule composed of a heterodimer of both heavy- and light-chain variable domains was produced by the construction of the expression vector mpSV2neo-EP1-Fv72.3. This vector contained the neo gene as a selection marker, the murine immunoglobulin heavy chain promoter (P1), enhancer (E), the SV40 polyadenylation signal region, and the murine cDNA fragments of VH and VL regions amplified and cloned directly from the B72.3 hybridoma RNA by the polymerase chain reaction technique. Termination codons were introduced into the 3' end of both VH and VL regions. The expression vector was transfected into the SP2/0 cell line. The Fv72.3 molecules were purified by the rabbit anti-B72.3 idiotype antibody affinity column, and retained the binding reactivity for the TAG72 antigen. The small size of Fv72.3 molecule (25 kD) makes it attractive for structural studies and immunodetection of cancers.
Mol Biother 1992 Jun
PMID:Genetic engineering of anticolorectal carcinoma Fv molecule in myeloma cells. 151 97

Serum samples from 13 blood group little p individuals were tested by radioimmunoassay for their IgG antibody subclass distribution against the P, P1 and Pk antigens. There was no uniform subclass distribution pattern, although all but one had IgG3 antibodies against all the P system antigens tested. Studies were performed adsorbing anti-Tja serum sequentially to columns with synthetic carbohydrate antigenic determinants within the P system coupled to silica beads (SynsorbsR). The effect on agglutinin and indirect antiglobulin titers was determined after adsorption to SynsorbsR with different P-system antigens (P1, Pk, P). Adsorption to all the three SynsorbsR was needed to eliminate or strongly reduce antibody titers. The effect on IgM, IgG, IgA as well as IgG subclass antibody binding to P, P1 and Pk antigens was also determined by radioimmunoassay and chromatogram binding assay. Anti-PP1Pk antibodies from a little p woman with repeated abortions were shown to bind to glycosphingolipid antigens prepared from one of the aborted placentae using a chromatogram binding assay. This binding was eliminated by serum adsorption to SynsorbsR with P1, Pk and P carbohydrates. Anti-PP1Pk antibodies were also shown to bind to extended structures in the globoseries, i.e. globopentaosylceramide, globohexaosylceramide (globo-H) and globoheptaosylceramide (globo-A). This binding is most probably due to antibodies recognizing internal sequences in the carbohydrate chain. Attempts were made to visualize the binding epitope of the antibodies by computer molecular modelling.
Mol Immunol 1992 Oct
PMID:Serological and immunochemical characterization of anti-PP1Pk (anti-Tja) antibodies in blood group little p individuals. Blood group A type 4 recognition due to internal binding. 152 96

Important mammalian defensive functions such as phagocytosis are triggered in leukocytes by the interaction of the Fc region of IgG with cell surface receptors (Fc gamma R). The CH2 domain of IgG has been implicated previously as the site of interaction with human and mouse Fc gamma R. This domain was mapped for interaction with mouse Fc gamma R11 expressed by the macrophage-like cell line P388D1, using two panels of a total of 32 site-directed mutants of mouse IgG2b and chimeric human IgG3 monoclonal antibodies. Two potential binding sites have been identified: one in or within the vicinity of the lower hinge site on IgG for human Fc gamma R1, and one within the binding site on IgG for Clq. The three mutant IgGs (Gly 237----Ala, Asn 297----Ala, and Glu 318----Ala) which do not interact in complexed form also fail to bind as monomers. A 1H NMR study of the three non-binding monomeric mutants suggests that the mutations are largely site-specific, indicating that IgG interacts with mouse Fc gamma R11 at two regions within the CH2 domain. This interaction dictates phagocytosis mediated by Fc gamma R11 of the P388D1 cell line.
Mol Immunol 1992 Jan
PMID:Multiple binding sites on the CH2 domain of IgG for mouse Fc gamma R11. 153 Sep 84

In the present study 3-iodo-4-hydroxy-5-nitrophenacetyl (NIP)-specific antibodies were compared for induction of antibody dependent lysis of NIP-derivatised red blood cells effected by pre-stimulated U937 or HL-60 cells and by K cells. The chimaeric antibodies have heavy chains corresponding to human IgG subclasses 1-4, and include site-directed mutants of IgG3 as well as the aglycosylated form of IgG3; a mouse IgG2b antibody and a site-directed mutant IgG2b were also examined. rIFN stimulated U937 or HL-60 cells express increased levels of Fc gamma R1 compared to unstimulated cells; PMA stimulated HL-60 and U937 cells express an increased level of Fc gamma R11 compared to unstimulated cells; K cells express Fc gamma R111. Using these effector cell populations and the target cells mentioned above, we have compared anti-NIP antibodies with different heavy chain constant domains for their ability to induce ADCC through human Fc gamma R1, Fc gamma R11 and Fc gamma R111. The results suggest that all three human Fc gamma receptors appear to recognise a binding site on IgG within the lower hinge (residues 234-237) and trigger ADCC via this site, but that each receptor sees this common site in a different way. The possibility that other amino acid residues also participate in the binding/triggering site(s) cannot be excluded.
Mol Immunol 1992 May
PMID:Mapping and comparison of the interaction sites on the Fc region of IgG responsible for triggering antibody dependent cellular cytotoxicity (ADCC) through different types of human Fc gamma receptor. 153 98

A matched set of chimeric mouse-human NP-antibodies were studied for the capacity to induce cell mediated cytotoxicity (ADCC) by normal peripheral blood NK/K cells. The target cells were sheep red blood cells (SRBC) sensitized with the haptens NP or NIP. All four IgG subclasses and several IgG3 variants with altered hinge were tested for ADCC activity. The hierarchy of the ADCC capacity among the subclasses was found to be IgG3 greater than IgG1 greater than IgG4 greater than IgG2. The superiority of IgG3 was only revealed at low effector cell:target cell ratio. The ADCC activity was for the most part unaltered by shortening the hinge region of IgG3 from 62 to 15 amino acids. Also, when the hinge region of IgG3 was mutated to become identical to that of IgG4, the ADCC activity was mainly unchanged. However, an IgG3 variant with deletion of all four hinge exons showed a depressed ADCC activity compared to the wild type. The IgG subclass pattern of complement-mediated lysis (CML) and ADCC is different and the capacity to induce CML and ADCC is changed differently by hinge region modification. Thus CML and ADCC have different structural requirements in the Fc region of IgG.
Mol Immunol 1992 Mar
PMID:Antibody dependent cell-mediated cytotoxicity induced by chimeric mouse-human IgG subclasses and IgG3 antibodies with altered hinge region. 155 42


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