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M Reth

Publications and source records attributed to M Reth.

88 records · Page 5Linked to original sources
PubMed1988

Transfected plasmacytoma cells do not transport the membrane form of IgM to the cell surface.

Expression vectors coding for membrane-bound IgM antibodies were introduced into myeloma and B lymphoma cells. Only the lymphoma but not the myeloma cells were able to express the antibodies on the cell surface, although in both cases, complete antibodies were assembled intracellularly. In myeloma cells, the Ig molecules did not reach the Golgi compartment. Thus, the intracellular transport of membrane-bound antibodies is controlled in the B cell lineages in a developmentally ordered fashion.

Animals↗
PubMed1988

A novel 34-kd protein co-isolated with the IgM molecule in surface IgM-expressing cells.

Plasmacytoma cells, transfected with a vector encoding a membrane-bound IgM molecule, do not show cell surface IgM expression, although complete IgM molecules are assembled intracellularly. The isolation of a surface IgM-positive variant allowed us to analyse molecular requirements of surface IgM expression. Only in surface IgM-positive cells, a 34-kd protein (B34) was found to be associated with IgM. B34 is a glycoprotein which forms a disulphide-linked homodimer. The surface IgM-positive variant cell line expressing B34 also contains transcripts of the pre-B and B cell specific mb-1 gene. The data are discussed in the context of a possible IgM-antigen receptor complex.

B-Lymphocytes↗
PubMed1987

Activation of V kappa gene rearrangement in pre-B cells follows the expression of membrane-bound immunoglobulin heavy chains.

During B cell development V kappa gene rearrangement seems to occur only in mu-positive pre-B cells. To study the role of the mu chain in the activation of the Ig kappa locus, we introduced expression vectors carrying different forms of the mu gene into null pre-B cells. The activation of the Ig kappa locus followed the expression of the membrane form (micron) of the mu chain. The expression of the secreted form (microS) did not result in the activation of the Ig kappa locus. We further show that both forms of the mu chain differ in their intracellular transport in pre-B cells.

Alleles↗
PubMed1984

Fc-dependent effector functions of idiotype-anti-idiotype immune complexes.

Some effector functions of antigen-antibody and antibody-antibody (idiotype-anti-idiotype) complexes were analyzed. As a model system a monoclonal IgM antibody specific for the hapten NP (antibody B1-8) was reacted either with hapten and hapten-carrier conjugates or with monoclonal anti-idiotope antibodies with specificity for B1-8 idiotopes. The precipitating, C1q-binding, complement-activating and Fc receptor binding properties of these complexes were compared. Binding of both hapten-carrier conjugates and anti-idiotope antibodies to B1-8 results in formation of complexes which depending on the B1-8:ligand ratio precipitate, activate complement, bind C1q and exhibit increased avidity for Fc mu and Fc gamma receptors of mouse spleen cells. In both types of complexes cross-linking of IgM molecules is essential for triggering these Fc-dependent functions, and a functional heterogeneity if idiotype-anti-idiotope complexes based on different idiotype-anti-idiotope ratios could also be observed. The functional similarity of B1-8-hapten-carrier and B1-8-anti-idiotope complexes suggests that regulatory functions so far assigned to antigen-antibody complexes could be carried out also by idiotype-anti-idiotope complexes.

Animals↗
PubMed1982

Somatic variants of murine immunoglobulin lambda light chains.

Studies of the murine lambda light chains produced by myeloma cells provided the first evidence for somatic point mutation of germ-line variable (V) region genes. An examination of the variable regions of 19 lambda 1 chains revealed seven which differed from a common sequence by one to three amino acid substitutions. Subsequently, one of these presumed somatic variants of the single lambda 1 V gene was characterized by DNA sequence analysis of the rearranged functional gene. The predicted DNA sequence alteration was observed and no silent mutation was evident. These studies of lambda chain variants suggested that the hypervariable, complementarity-determining regions (CDRs) ht be a preferred site of somatic mutation because all seven characterized variants contained substitutions only in these regions. By contrast, comparisons of closely related kappa chain variable region amino acid sequences, and more recently VK and VH genes, have suggested that somatic mutation probably occurs in codons for both framework and CDR residues. To examine this apparent discrepancy between the sites of somatic mutations in lambda and kappa genes, we have determined the nucleotide sequence of two lambda 1 gene from hybridomas and a lambda 2 gene from a myeloma. These sequences demonstrate that somatic mutation in lambda genes can occur in both the framework and CDR residues.

Amino Acid Sequence↗
PubMed1982

The immune response against anti-idiotope antibodies. I. Induction of idiotope-bearing antibodies and analysis of the idiotope repertoire.

In the present analysis we dissect the idiotype repertoire, independently of hapten-binding specificity, by immunizing different strains of mice with cross-linked monoclonal anti-idiotope antibodies against antibody B1-8. B1-8 is a monoclonal antibody with specificity for the hapten (4-hydroxy-3-nitro-phenyl)acetyl (NP) and carries a germ line gene-encoded variable region. The results demonstrate that the expression of B1-8 idiotopes and their association with each other and with NP-binding specificity are strain-specific. Certain idiotopes are expressed on antibodies differing in antigen-binding specificity, whereas one of the idiotopes appears strictly associated with NP-binding antibodies. The genetic analysis provides strong evidence that the strain specificity of the idiotope repertoire is a result of V region polymorphism in the mouse.

Animals↗
PubMed1981

Control of idiotope expression by monoclonal anti-idiotope and idiotope-bearing antibody.

Preinjection of C57BL/6 mice with nano-to microgram amounts of a monoclonal IgG1 antibody directed against a binding site-related idiotope of the anti-NP [(4-hydroxy-3-nitro-phenyl)acetyl] antibody B1-8 results in enhancement or suppression of the corresponding and of another B1-8 idiotope in a subsequent anti-NP response, depending on the dose of the injected anti-idiotope antibody. The enhancing and suppressive effects appear two weeks after anti-idiotope administration and are maximal after 6-8 weeks. They are predominantly expressed at the level of IgG, not IgM, antibodies. Enhancement of idiotype expression, i.e. idiotypic memory, can also be induced by the injection of idiotypic antibody of the IgM class, namely antibody B1-8. This effect might represent one of the general mechanisms by which immunological memory is established.

Animals↗
PubMed1981

Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region.

To examine germ line genes of the heavy chain variable region (VH) that might contribute to formation of antibodies of the NPb family, we have derived cDNA clones from two hybridomas making NPb antibodies. One, B1-8, made an IgM protein and was derived during a primary response; the other, S43, made an IgG2a protein and was derived during a hyperimmune response. Sequence comparison of the two clones showed that they differed by only 10 bp in the VH region, had very different D segments and had identical J segments (J2). A set of closely related germ line VH genes was then cloned from a partial Eco RI library of C57Bl/6 DNA. By comparing the germ line VH regions to the cDNA VH regions, we identified seven potential candidates for encoding the VH regions of NPb antibodies. The seven VH regions were sequenced, and one V(186-2) contained exactly the DNA sequence found in the clone derived from B1-8. None of the DNA sequence differences that distinguished the S43-derived clone from the B1-8 clone was found in any of the other six germ line genes. Because the S43 sequence was more closely related to the V(186-2) germ line sequence than to any of the other VH genes, we conclude that the differences between the genes resulted from somatic mutation and that the two hybridomas derived their VH regions from the same germ line gene. Certain of the sequenced VH genes contain crippling mutations; the repertoire of germ line VH genes that can contribute to the diversity of antibodies may therefore be less than the total number of genes detectable by hydridization.

Animals↗
PubMedDate not supplied

A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production.

During B-cell development, the VH genes of immunoglobulin heavy (H) chains are assembled from three different germline components: the variable (VH) segment, the diversity (D) segment and the joining (JH) segment. The joining between two segments involves the recognition of conserved nonamer-heptamer sequences bordering each segment, double-stranded cuts at the heptamer-segment border, and the re-ligation of the two segment ends which have frequently been modified by the deletion and addition of nucleotides. The flexibility of the joint increases VHDJH variability. However, it also results in many pre-B cells which do not produce immunoglobulin H chains and have non-functional VHDJH complexes carrying the VH and JH coding sequences in different reading frames. We show here that such 'null cells' are not dead-end products of the B-cell developmental pathway but can perform a novel VH to VHDJH joining using a 5' VH segment to replace the VH sequence of the VHDJ-H complex. This process can result in the generation of a VHDJ+H complex and the subsequent expression of an immunoglobulin heavy chain.

Animals↗