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M Reth

Publications and source records attributed to M Reth.

At least 73 records · Page 4Linked to original sources
PubMed1992

Antigen receptors on B lymphocytes.

Recent studies on the structure of the B cell antigen receptor demonstrate that the membrane-bound and antigen-binding immunoglobulin molecules are noncovalently associated with a heterodimer of two novel transmembrane proteins. The B cell antigen receptor is thus a multicomponent receptor complex whose structural features are similar to those of the T cell antigen receptor complex. Cross-linking of the B cell antigen receptor results in rapid tyrosine phosphorylation of substrate proteins. This suggests that the B cell receptor belongs to a subgroup of the tyrosine kinase receptor family with a noncovalently associated src-like tyrosine kinase.

Amino Acid Sequence↗
PubMed1991

Cell surface expression of the short immunoglobulin mu chain (D mu protein) in murine pre-B cells is differently regulated from that of the intact mu chain.

Pre-B cells carrying DJH rearrangements in an appropriate reading frame produce a short mu protein consisting of a DJH and the C mu & sequence (D mu protein). We analyzed a D mu-producing Abelson-murine leukemia virus-transformed murine pre-B line, 300-19, and demonstrated that D mu proteins are expressed on the cell surface in association with surrogate L chain proteins (lambda 5 and VpreB). However, when we introduced an expression vector coding for the D mu protein into the null pre-B line P17-27, which produce lambda 5 and VpreB but no Ig molecules, most of the cells did not express D mu proteins on the cell surface although D mu proteins were produced intracellularly. On the other hand, P17-27 brings intact mu chains on the cell surface, when a vector coding for the intact mu chain is introduced. Thus, cell surface expression of the D mu protein has different requirements from that of the intact mu chain. A possible role of the VH protein encoded by germ-line VH transcripts is discussed.

Animals↗
PubMed1991

The B cell antigen receptor of class IgD can be expressed on the cell surface in two different forms.

Membrane-bound immunoglobulins of the IgM and IgD class are expressed on the B cell surface in association with a disulfide-linked heterodimer consisting of alpha and beta subunits. While the alpha component of the IgM antigen receptor (IgM-alpha, 34 kDa) is encoded by the B cell-specific gene mb-1, the gene coding for IgD-alpha (35 kDa) has not yet been identified. We show here that the alpha component of the IgD antigen receptor is also encoded by the mb-1 gene. The difference in molecular weight between IgM-alpha and IgD-alpha thus seems to be due to post-translational modifications of the mb-1 gene product. We also demonstrate that the previously described myeloma variant J558L delta m2.6 expresses an alternative form of the IgD antigen receptor, which does not contain an alpha/beta heterodimer.

Animals↗
PubMed1990

The products of pre-B cell-specific genes (lambda 5 and VpreB) and the immunoglobulin mu chain form a complex that is transported onto the cell surface.

We constructed expression vectors coding for the two pre-B-specific genes, VpreB and lambda 5, and transfected them together with a mu vector (mu tm) into Ig- myeloma cells. In a transfectant expressing all three introduced genes, the mu tm chain is transported on the cell surface. A biochemical analysis demonstrated that, in these cells, the mu tm chain is associated noncovalently with an 18-kD protein and covalently with a 22-kD protein, which are most likely the products of VpreB and lambda 5, respectively. Our results, thus, strongly suggest that the products of lambda 5 and VpreB bind to mu chains and have the same capacity as conventional Ig L chains to allow surface expression of mu chains.

Animals↗
PubMed1990

Membrane IgM and IgD molecules fail to transduce Ca2+ mobilizing signals when expressed on differentiated B lineage cells.

We have measured Ca2+ mobilization in a panel of B lineage cell lines after stimulation with anti-Ig to assess whether membrane Ig transduces a functional signal in cells that are representative of immature, mature, or terminally differentiated stages. For these studies, three transfected cell lines which express the same IgM molecule (300-19 microns lambda 36/8, K46-17 microns lambda, and J558L microns lambda 3) as well as two lines expressing an identical IgD molecule (K46 delta m2.6 and J558L delta m8.8) were used. Cross-linking of membrane Ig on IgM+ or IgD+ lymphomas (K46-17 microns lambda or K46 delta m2.6) resulted in a Ca2+ mobilization response that is similar to that seen in mature, resting B cells. Both intracellular release and extracellular influx of Ca2+ were observed. In contrast, ligation of membrane Ig on an IgM+ pre-B cell line (300 - 19 microns lambda 36/8) induced extracellular influx of Ca2+ but no detectable intracellular release. Finally, cross-linking of membrane Ig on IgM+ or IgD+ plasmacytomas (J558L microns 3 or J558L delta m8.8) or an IgD+ B cell hybridoma (B1.8.delta 1) expressing an endogenous Ig gene, did not result in a detectable Ca2+ mobilization response. Importantly, stimulation of cells with the GTP-binding protein activator, aluminum fluoride, resulted in a comparable Ca2+ mobilization response in all cell lines. In view of the fact that aluminum fluoride induced a Ca2+ response in the terminally differentiated B cell lines, J558L microns 3, J558L delta m8.8, and B1.8.delta 1, it is likely that there is an alteration in the signal transduction cascade at some point proximal to GTP binding protein activation. This finding suggests that differentiation of the B cell is accompanied by the loss or alteration of one or more components that couple membrane Ig to subsequent signal transduction elements. Finally, it has previously been demonstrated that the IgM+ cell lines described above, express the recently described membrane Ig-associated protein, B34. Thus, it is apparent based on the fact that the J558L microns 3 cell line does not mobilize Ca2+ after stimulation with anti-Ig, that coexpression of B34 in association with membrane Ig does not constitute a functional receptor complex capable of activating GTP-binding proteins that in turn regulate Ca2+ mobilization.

Aluminum↗
PubMed1990

Molecular components of the B-cell antigen receptor complex of the IgM class.

The antigen receptors on mature B lymphocytes are membrane-bound immunoglobulins of the IgM and IgD classes whose cross-linking by polyvalent antigens results in B-cell proliferation and differentiation. How these membrane-bound immunoglobulin chains, which lack a cytoplasmic tail, generate a cell activation signal is not at present known. We now show that the IgM molecule is non-covalently associated in the membrane of B cells with two proteins of relative molecular mass 34,000 (Mr 34 K; IgM-alpha) and 39 K (Ig-beta) which form a disulphide-linked heterodimer. Surface expression of IgM seems to require the formation of an appropriate complex between IgM and the heterodimer. A transfection experiment indicates that IgM-alpha is the product of mb-1, a B-cell specific gene encoding a transmembrane protein with sequence homology to proteins of the T-cell antigen receptor-CD3 complex.

Animals↗
PubMed1990

A physical map and analysis of the murine C kappa-RS region show the presence of a conserved element.

Lambda-producing B lymphocytes have frequently deleted one or, more often, both Ig kappa loci. This deletion is mediated by the rearrangement of an element which lies 3' of C kappa and which is called RS (recombining sequence) in the mouse and Kde (kappa-deleting element) in the human. The tight correlation between V lambda to J lambda rearrangements and an RS-mediated deletion may indicate that sequences in the C kappa-RS region are controlling the activation of the Ig lambda locus. We have linked the C kappa exon and the RS element by phage cloning and compared the C kappa-RS region to the previously cloned human C kappa-Kde region. The distance between C kappa and RS is 25 kb and is thus similar to the distance of 24 kb separating the human C kappa exon and Kde element. Both mouse and man carry a conserved sequence of 470 bp (Rx) which lies 9 kb 3' of the mouse C kappa and 12 kb 3' of the human C kappa exon. The conserved mouse Rx sequence contains part of the kappa 3' enhancer.

Animals↗
PubMed1990

Identification of the genes encoding the IgM-alpha and Ig-beta components of the IgM antigen receptor complex by amino-terminal sequencing.

Beside the immunoglobulin (Ig) heavy and light chains the murine B cell receptor of the IgM class contains a heterodimer of two transmembrane proteins (IgM-alpha and Ig-beta). By N-terminal sequencing of IgM-alpha and Ig-beta we have identified the genes encoding these proteins as mb-1 and B29, respectively. Both genes are B cell specific and have been previously cloned from B minus T cell subtractive cDNA libraries. We have constructed expression vectors of the two genes and demonstrate that expression of the mb-1 and B29 genes can influence the surface expression of IgM in micron-transfected myeloma cells. From the known sequences of the IgM-alpha and Ig-beta proteins and from the results of previous transfection experiments with various vectors expressing the mu chain we have developed a structural model of the B cell antigen receptor of class IgM which we compare with that of the T cell antigen receptor.

Amino Acid Sequence↗
PubMed1990

Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM.

Two classes of immunoglobulin, IgM and IgD, are present as antigen receptors on the surface of mature B lymphocytes. We show here that IgD molecules are noncovalently associated in the B cell membrane with a heterodimer consisting of two proteins of 35 kd (IgD-alpha) and 39 kd (Ig-beta), respectively. The two novel proteins are not found in the IgD-expressing myeloma J558L delta m, which fails to bring IgD antigen receptor onto the cell surface. In a surface IgD positive variant line of this myeloma, however, membrane-bound IgD molecules are associated with the heterodimer, suggesting that the formation of an antigen receptor complex is required for surface IgD expression. We further demonstrate that the IgD-associated heterodimer differs partly from that of the IgM antigen receptor and that its binding to the heavy chain only requires the presence of the last constant domain and the transmembrane part of the delta m chain.

Animals↗
PubMed1989

A novel germ-line JK transcript starting immediately upstream of JK1.

Germ-line transcripts of the immunoglobulin (Ig) and T cell receptor loci are thought to be involved in the control of V gene rearrangement by rendering these loci accessible to the recombinases. We have analyzed the transcriptional activity of germ-line K alleles in two bone marrow-derived Abelson-murine leukemia virus transformed pre-B cells: 300-19, a null cell line, and P8 a mu-producing line. We found a novel germ-line JK transcript starting immediately upstream of JK1 and spliced to CK. The potential role of this transcript in the opening of the Ig K locus as well as in the ordered usage of JK segments is discussed.

Animals↗
PubMed1989

Membrane-bound IgM obstructs B cell development in transgenic mice.

Rearranged immunoglobulin genes encoding either the secreted (microsecond) or membrane (micron) form of IgM were introduced into the mouse germ line. We report here the phenotypic analysis of lymphocyte populations in these mice (T microsecond and T micron). In T microsecond mice the transgenic mu chain is present in serum antibodies. The frequencies of B cells in the various B cell compartments of T microsecond mice are normal or slightly reduced compared to littermates. In T micron mice, however, B cell (but not T cell) development is severely affected. Spleens of 8-week-old T micron mice contain about 3%-8% B cells, increasing to approximately 20% at the age of 8 months. These cells express endogenous IgM. B cells expressing only transgenic micron chains are not detectable. In the bone marrow B cells are almost completely depleted. A B cell population characterized by reduced levels of IgD on the cell surface is enriched in the spleen and present at almost normal levels in the peritoneum of T micron mice.

Animals↗
PubMed1988

Ordered activation of the Ig lambda locus in Abelson B cell lines.

Derivatives of the mu-producing Abelson line P8 have been analyzed for L chain gene rearrangements. Two of seven clones studied assembled their V lambda genes while growing in culture. V lambda gene rearrangements occurred only in those Abelson subclones that either were rearranging or had rearranged their recombining sequence (RS) element on both Ig kappa alleles. Our data suggest that (a) RS rearrangements are preferentially initiated in kappa- pre-B cells; and (b) the deletion or inactivation of sequences lying between J kappa and RS is a requirement for the activation of the Ig lambda locus.

Abelson murine leukemia virus↗