Disease relevance of Igh-V3609N

• We have shown previously that genes activated by the immunoglobulin heavy chain (IgH) enhancer or promoter in mouse myeloma cells are extinguished upon fusion of the myeloma with a mouse T cell lymphoma [1].
• We have determined the sequence of the normal human c-myc gene and compared it to portions of a c-myc gene that has been translocated into the immunoglobulin heavy chain locus in a Burkitt lymphoma cell [2].
• To define the contribution of the normal SWR strain to the development of nephritis, we analyzed the association of the I-A beta-chain gene of Ia-encoding region, the T-cell-receptor beta (TcR beta)-chain gene, and immunoglobulin heavy-chain allotype (IgH) with the development of lupus nephritis in 165 NZB X SWR crosses [3].
• We describe the purification to apparent homogeneity of the murine immunoglobulin heavy-chain (IgH) enhancer-binding protein mu EBP-E from murine plasmacytoma cells by ion exchange and affinity chromatography [4].
• Follicular lymphoma (FL) is characterized in a significant proportion of cases by the t(14;18) chromosomal translocation, which results in the juxtaposition of the oncogene bcl-2 to the joining region of the immunoglobulin heavy chain (IgH) gene [5].

Psychiatry related information on Igh-V3609N

• A retroviral vector, RIM, containing murine c-myc under the control of immunoglobulin heavy-chain gene promoter and enhancer elements and v-Ha-ras driven by a Moloney murine leukemia virus long terminal repeat induced IgM-secreting plasmacytomas in 28% of adult and 83% of 3-week-old pristane-conditioned mice with mean latency periods of 60-70 days [6].

High impact information on Igh-V3609N

• Gene targeting experiments have demonstrated that the expression of immunoglobulin heavy chain in the pre-B cell receptor (pBCR) and of heavy and light chains in the B cell antigen receptor (BCR) marks checkpoints in early B cell development that the cells have to pass to survive [7].
• A programmed translocation between the c-myc and immunoglobulin heavy chain genes on chromosomes 15 and 12 was created by this method [8].
• In productively rearranged murine VH-DH-JH genes (encoding immunoglobulin heavy chain variable regions), the DH elements are preferentially used in one particular reading frame (RF1), although the recombination breakpoints at the DH-JH border vary [9].
• The endogenous immunoglobulin heavy chain locus resides on mouse chromosome 12, which shows that transgene isotype switching can occur between two different chromosomes even though normal antibody gene switching has generally been thought to occur within one chromosome [10].
• The present study shows that positive regulatory trans-acting factors are involved in the activation of the immunoglobulin heavy chain gene through its enhancers and are contained only in cells of the B lineage [11].

Biological context of Igh-V3609N

• Immunoglobulin (Ig) class switching is initiated by deamination of C-->U within the immunoglobulin heavy chain locus, catalyzed by activation-induced deaminase (AID) [12].
• The mouse immunoglobulin heavy-chain enhancer: effect on transcription in vitro and binding of proteins present in HeLa and lymphoid B cell extracts [13].
• The ability of the mouse immunoglobulin heavy chain gene (IgH) enhancer to stimulate in vitro transcription from the adenovirus-2 major late promoter (Ad2MLP) has been investigated [13].
• B cells expressing a natural polyreactive autoantibody have a distinct phenotype and are overrepresented in immunoglobulin heavy chain transgenic mice [14].
• Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells [15].

Anatomical context of Igh-V3609N

• Transcriptional competence of the immunoglobulin heavy-chain locus (IgH) is established at an early stage of lymphoid cell development, leading to the appearance of RNA components, previously called C mu RNA1 or sterile-mu RNA2, which contain constant-region sequences but lack variable-region sequences [16].
• The increase in abundance of immunoglobulin heavy-chain (IgH) mRNA that accompanies development of a B cell into a plasma cell is mainly due to post-transcriptional events [17].
• As shown by PCR analyses, the pre-BI cells in Pax5-deficient bone marrow have undergone D(H)-to-J(H) rearrangement of the immunoglobulin heavy-chain locus at normal frequency [18].
• The mouse immunoglobulin heavy-chain (IgH) B-lymphocyte enhancer stimulates transcription from heterologous promoters 20- to 40-fold when transfected into several non-lymphoid cell lines [19].
• Complete immunoglobulin heavy chain (IgH) genes (gamma and mu) containing the intronic IgH enhancer and mutations in the upstream promoter region were constructed in vitro and introduced into murine J558L myeloma cells by protoplast fusion [20].

Associations of Igh-V3609N with chemical compounds

• Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements [21].
• Stimulation of small, resting, splenic B cells with bacterial lipopolysaccharide (LPS) induces proliferation, differentiation to plasma cell formation, and the expression of immunoglobulin heavy chain (IgH) [22].
• Tyrosine and glycine constitute 40% of complementarity determining region 3 of the immunoglobulin heavy chain (CDR-H3), the center of the classic antigen-binding site [23].
• In B cells, but not in pre-B cells, the membrane immunoglobulin heavy chain is post-translationally converted to a relatively hydrophobic form that partitions into the oil phase when solubilized with the phase-separating detergent Triton X-114 [24].
• Proteins binding to site C2 (muE3) in the immunoglobulin heavy-chain enhancer exist in multiple oligomeric forms [25].

Physical interactions of Igh-V3609N

• We report the isolation and characterization of cDNA clones that encode a protein with the same DNA binding specificity as the immunoglobulin heavy chain enhancer binding protein E (muEBP-E) [26].
• Transcription factor E3 (mTFE3) is a murine transcription activator that binds to the intronic enhancer of the immunoglobulin heavy chain gene [27].
• When Pax5 binding to the enhancer in B cells was blocked in vivo by transfection with a triple-helix-forming oligonucleotide an alpha P footprint appeared and endogenous immunoglobulin heavy chain transcripts increased [28].
• Previous studies have demonstrated that BCL-6 and Stat6 can both bind and regulate the Iepsilon promoter that controls immunoglobulin heavy chain class switching to IgE [29].
• Recent studies have established genetic linkage between iv and the immunoglobulin heavy chain gene complex (Igh-C), located on distal mouse chromosome 12 [30].

Enzymatic interactions of Igh-V3609N

• Complementation of RAG-2-deficient blastocysts with mutant ES cells heterozygous for a targeted mutation that deletes all immunoglobulin heavy-chain joining (JH) gene segments (JH+/-) also leads to generation of chimeras with normal B and T cells [31].

Regulatory relationships of Igh-V3609N

• Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene [32].
• We have generated transgenic mouse lines that carry one of three different constructs in which the murine N-myc gene is expressed under the control of the immunoglobulin heavy chain transcriptional enhancer element (E mu-N-myc genes) [33].
• Regulatory elements in the immunoglobulin heavy chain gene 3'-enhancers induce c-myc deregulation and lymphomagenesis in murine B cells [34].
• Rearrangement of immunoglobulin heavy-chain variable (V(H)) gene segments has been suggested to be regulated by interleukin 7 signaling in pro-B cells [35].
• Cux/CDP homeoprotein is a component of NF-muNR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator [36].

Other interactions of Igh-V3609N

• The control of the development of anti-Sm in individual MRL/lpr mice has been shown to be the result of stochastic factors, and previous research has indicated that the immunoglobulin heavy chain (IgH) b allotype may be more amenable to the production of anti-Sm [37].
• Hsp86-1 was mapped 11.6 cM from the immunoglobulin heavy chain gene IgH on Chromosome 12 using an intersubspecies backcross [38].
• Gene targeting in mouse embryonic stem (ES) cells was used to replace (i) the mouse immunoglobulin heavy chain (IgH) Cgamma2a gene segment (mCgamma2a) with the human Cgamma1 gene segment (hCgamma1), and (ii) the mouse immunoglobulin light chain (IgL) Ckappa gene segment (mC kappa) with its human counterpart (hC kappa) [39].
• Compared with untransfected and sense controls, significant decreases in IgM secretion (and RNA levels) were detected in clones transfected with antisense constructs utilising the mouse metallothionein-1 promoter and the immunoglobulin heavy chain intronic enhancer elements [40].
• A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes [41].

Analytical, diagnostic and therapeutic context of Igh-V3609N

• To further understand how B-cell-specific immunoglobulin promoter expression is mediated, the murine lymphoid cell line 2017 was engineered to express the green fluorescent protein under the control of an immunoglobulin heavy chain promoter and selected for high activity using multiple rounds of fluorescence-activated cell sorting [42].
• We grafted childhood B-precursor acute lymphoblastic leukemia (ALL) bone marrow (BM) cells into mice with severe combined immunodeficiency (SCID), in order to study the clonal evolution of immunoglobulin heavy chain (IgH) rearrangements in the absence of selective pressure by chemotherapy [43].
• The specific developmental stage of each line was determined using Southern blot analysis to ascertain their rearrangement status at the immunoglobulin heavy chain locus (DJ/DJ, VDJ/DJ or VDJ/VDJ) [44].
• Lymphomas were assessed by serial morphologic techniques, immunohistochemistry, flow cytometry, and analysis of T cell receptor (TCR) or immunoglobulin heavy chain (IgH) gene rearrangements [45].
• Abnormalities in the glycosylation of immunoglobulin heavy chain and an h-2 transplantation antigen in a mouse myeloma mutant [46].

References