Disease relevance of Igh

• Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice [1].
• We conclude that Myc(His) insertion into Igh predictably induces B-cell and plasma-cell tumors in mice, providing a valuable mouse model for understanding the transformation-inducing consequences of the MYC/Myc-activating endemic Burkitt lymphoma t(8;14)/plasmacytoma T(12;15) translocation [2].
• Thus, our characterization of the region 5' of the VH gene cluster demonstrated the presence of a single cluster of DNase I hypersensitive sites within the 5' flanking region, and identified a candidate Igh regulatory region defined by pro-B cell-specific hypersensitivity and interaction with factors implicated in regulating VDJ recombination [3].
• T-cell responsiveness to LCMV segregates as a single locus in crosses between BALB/cA and C.B-17 mice. Evidence for regulation by a gene outside the Igh region [4].
• The course of systemic infection with lymphocytic choriomeningitis virus (LCMV) was studied in BALB/cA and C.B-17 mouse strains differing in the immunoglobulin heavy chain region (Igh) [4].

Psychiatry related information on Igh

• These data demonstrate a selective genetic linkage of discrete T15 Id determinants, AB1-2 and B36-82 with the Igh allotype [5].

High impact information on Igh

• Nucleic acid hybridization studies suggest that 500-1000 or more heavy chain variable (VH) gene segments related to one VH gene segment (J558) are present in the genome of the BALB/c mouse [6].
• Localization of Nbs1 and gamma-H2AX to the Igh locus during CSR is dependent on AID [7].
• Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro but do not show a propensity for spontaneous tumorigenesis [8].
• In contrast, an analogous myc transgene, designed to mimic the myc-Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells [8].
• The putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas [8].

Chemical compound and disease context of Igh

• Mesangial glomerulonephritis was induced in mice by intravenous injection of preformed soluble immune complexes of dextran sulfate and either IgA (J 558) or IgM (MOPC 104 E) anti-dextran MAb (passive model) or by immunization with DEAE dextran (active model) [9].
• These studies examined the fate of Factor XIII (fibrin-stabilizing factor) in mice with plasmacytoma (MOPC-300, MOPC-384, MOPC-467, and J-558) [10].
• Among the TGB5 Id+, GT+ antibodies, which dominate the neonatal response to (T,G)-A-L, two VH gene families were used: J558 (high frequency) and 36-60 (low frequency) [11].
• Tumor cells treated in vitro with TSA showed delayed onset and rate of tumor growth in 70% of the J558 plasmacytoma and 100% of the B16 melanoma injected animals [12].
• More mature lymphomas (BAL-17, CH12 and CH27) and fully differentiated myelomas (J558 and MOPC-315) are insensitive to PGE2 [13].

Biological context of Igh

• Therefore, it can be suggested that the two genes coding for the T cell allodeterminants (distinct from those of the B cell Igh) are located in the right side of the B cell Igh-V on the 12th chromosome, and that both encode the antigen-recognition units of the functionally distinct T cell factors [14].
• The mouse T cell alloantigen, Tsud, is expressed on a minority of mature, Lyt-2+ cells, and its expression is controlled by a gene linked to the immunoglobulin heavy chain gene cluster, Igh [15].
• We used gene targeting in mice to insert a His(6)-tagged mouse c-Myc cDNA, Myc(His), head to head into the mouse immunoglobulin heavy-chain locus, Igh, just 5' of the intronic enhancer, Emu [2].
• Deletional mapping of fifteen mouse VH gene families reveals a common organization for three Igh haplotypes [16].
• The Igh locus is controlled by cis-acting elements, including Emu and the 3' IgH regulatory region which flank the C region genes within the well-studied 3' part of the locus [3].

Anatomical context of Igh

• Thus, isotypes encoded by genes on the 3' end of the Igh-gamma gene complex, which in the absence of T cells have a low probability of being switched to, are the most influenced by T cell help [17].
• C.B-20 ( Ighb ) mice challenged with BALB/c ( Igha ) spleen cells (or vice-versa) generate cytotoxic T lymphocytes (CTL) that recognize an antigen, H-40, controlled by an Igh-linked gene [18].
• Prior to rearrangement, Igh moves from its default peripheral location near the nuclear envelope to an interior compartment, and after rearrangement it returns to the periphery [19].
• Insertion of c-Myc into Igh induces B-cell and plasma-cell neoplasms in mice [2].
• Influence of Igh-linked gene products on the generation of T helper cells in the response to sheep erythrocytes [20].

Associations of Igh with chemical compounds

• To identify any sites in Igh responsible for its association with the periphery, we systematically analyzed the nuclear positions of the Igh locus in mouse non-B- and B-cell lines and, importantly, in primary splenic lipopolysaccharide-stimulated B cells and plasmablasts [19].
• Immunogenetics of BCG-induced anergy in mice. Control by Igh- and H-2-linked genes [21].
• After stopping anti-mu treatment of C.AL-20 mice, ABA-specific Ts repertoires undergo a defined expansion shown by their acquisition of an additional Ts network that displays Igh restrictions characteristic of normal C.AL-20 mice [22].
• Regulation of T15 idiotype dominance. II. Genes unlinked to the Igh locus regulate T15 dominance of the secondary adoptive transfer response to phosphocholine [23].
• Analysis of sera from AXC Igh recombinant mice maps the 91A3 marker to the left of Igh-Dex, consistent with the location of the VH genes controlling the arsonate CRI [24].

Physical interactions of Igh

• Taken together with results previously obtained, it is concluded that both major histocompatibility complex and Igh-linked genes affect the CTL specificity repertoire [25].
• Using a battery of congenic and inbred strains, it was shown that the QUPC52 idiotype was controlled by genes linked to the Igh complex locus (chromosome 12) and to the Ig kappa complex locus (chromosome 6) [26].
• Immunoglobulin heavy chain (Igh) locus rearrangements are controlled in part by an approximately 30 b complex 3' regulatory region located 3' of C alpha: this region contains several enhancers [27].

Regulatory relationships of Igh

• Identification of VH438, which shared VH hybridization pattern with 6% of a panel of 352 MRL/lpr hybridomas, suggests that the frequency of J558 use among spontaneously activated B cells in MRL/lpr mice is greater than previously reported [28].
• Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement [29].
• Igh-linked genes that influence BCG-induced splenomegaly were located on the centrometric side of the Igh-1 locus [30].
• The implication from replication timing studies in the B-cell line MPC11 was that early replication of the Igh locus was regulated by sequences downstream of the C alpha gene [31].
• Subsequent activation of the V(H) locus happens in at least three differentially regulated domains: an interleukin-7-regulated domain consisting of the 5' J558 family, an intermediate domain and the 3' V(H) genes, which are hyperacetylated in response to DJ(H) recombination [32].

Other interactions of Igh

• Genes coding for the determinants were shown to be accommodated somewhere in the right side of the Igh variable region gene (Igh-V) cluster, as the antibody activity was completely absorbed with BAB-14 thymocytes [14].
• The gene maps to the Igh-C region end of the Igh complex, telomeric to Tsu in the region of Pre-1 [18].
• The alloantiserum was raised in BALB/c (H-2d, Igh-1a) mice hyperimmunized with spleen cells of Igh allotype congenic mice, CB-20 (H-2d, Igh-1b) [14].
• Immunogenetics of BCG-induced anergy in mice: control by genes linked to the Igh complex [33].
• The data are consistent with the interpretation that the latter 5 strains do not process Igh-Gte genes and the Igh haplotypes of these strains represent examples of crossing over within the Igh complex [34].

Analytical, diagnostic and therapeutic context of Igh

• Comparison of consensus sequences of homologous autoantibodies and previously reported restriction mapping suggest that a minimum of three highly related J558 germ-line genes encode lupus autoantibodies [28].
• Furthermore, analysis by two-dimensional gel electrophoresis indicates that replication forks proceed exclusively in the 3'-to-5' direction through the region 3' of the Igh locus [31].
• Karyotyping of 70 Rb-carrying Pcts demonstrated that in these tumors, just as in their counterparts in inbred C mice, the Igh heavy-chain locus was translocated with Myc more often than was the Igk light-chain locus [35].
• Recently, structural genes of a transplantation antigen on the methylcholanthrene-induced sarcoma Meth A were mapped to the same region of chromosome 12 as the Igh gene complex [36].
• Subsequent V region sequence analysis of three of the anti-laminin Ab revealed that they in fact utilized a J558 VH gene (VH50) [37].

References