Disease relevance of Igh-6

• Characterization and development of T-Cell immune responses in B-cell-deficient (Igh-6(-/-)) mice with Salmonella enterica serovar Typhimurium infection [1].
• For this purpose, various genetically engineered immunodeficient mice were employed, including RAG-2 SCID, Igh-6 (B-cell deficient), Tcrb Tcrd (T-cell deficient) and Hc(0) (C5 deficient) [2].
• Deregulated expression of c-Myc in a translocation-negative plasmacytoma on extrachromosomal elements that carry IgH and myc genes [3].
• We show that pro-B lymphomas in mice deficient for both p53 and nonhomologous end-joining (NHEJ) contain complicons that coamplify c-myc (chromosome 15) and IgH (chromosome 12) sequences [4].
• The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma [5].

Psychiatry related information on Igh-6

• Locomotor activity as assessed by open-field test increased after KA administration in Igh-6(-/-) and wild-type mice only [6].
• The idiotopic (Id) repertoire of antibody response to phosphocholine was studied in mouse strains with different IgH allotypes [7].

High impact information on Igh-6

• Roles of IgH and L chains and of surrogate H and L chains in the development of cells of the B lymphocyte lineage [8].
• Here we report that AID is essential for the c-myc/IgH chromosome translocations induced by IL6 [9].
• AID is required for c-myc/IgH chromosome translocations in vivo [9].
• Complicon formation is initiated by recombination of RAG1/2-catalyzed IgH locus double-strand breaks with sequences downstream of c-myc, generating a dicentric (15;12) chromosome as an amplification intermediate [4].
• We replaced the IgH 3' enhancer (3'EH) region with a neomycin resistance gene in ES cells and generated chimeric mice in which all mature lymphocytes were either heterozygous (3'EH+/-) or homozygous (3'EH-/-) for the mutation [10].

Biological context of Igh-6

• We find that AID targets cytosines in both donor and acceptor switch regions (S regions) with the deamination domains initiating approximately 150 nucleotides 3' of the I exon start sites and extending over several kilobases (the IgH intronic enhancer is spared) [11].
• However, these Ras-RAG pre-B cells also upregulated surface markers characteristic of more mature B cell stages and populated peripheral lymphoid tissues, with an overall phenotype reminiscent of B lineage cells generated in a RAG- deficient background as a result of expression of an Ig mu HC together with a Bcl-2 transgene [12].
• 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 [13].
• Firstly we show that, in contrast to the murine BCP cells, the IL-7 response of human BCP-ALL cells did not correlate with the status of IgH chain gene rearrangement and expression, nor with the rearrangement of IgL chain genes [14].
• Early expression of Ig mu chain from a transgene significantly reduces the duration of the pro-B stage but does not affect the small pre-B stage [15].

Anatomical context of Igh-6

• In the present study, we examined the role of B cells in the development of Th1 T-cell responses to Salmonella by using gene-targeted B-cell-deficient mice (Igh-6(-/-) mice) [1].
• Histopathological analysis of the mice that survived 7 days after KA administration revealed that CD4/CD8(-/-) mice had the fewest pathologic changes but Igh-6(-/-) mice showed more severe lesions in area CA3 of the hippocampus than CD8(-/-) and wild-type mice [6].
• Their IgH loci are partly in germ-line, partly in DHJH-rearranged configuration, while their light chain loci are in germ-line configuration [16].
• Igh-6(-/-) mice were able to control a primary infection and to clear the inoculum from the reticuloendothelial system [17].
• Thus, the environment of fetal liver or bone marrow is not required for the pre-BCR to exert its function, which is to select and expand cells that have undergone an inframe V(H)-D(H)J(H) rearrangement that produces a pre-BCR-compatible muH chain [18].

Associations of Igh-6 with chemical compounds

• The roles of T cells and B cells in kainic acid (KA)-induced hippocampal lesions were studied in C57BL/6 mice lacking specific T cell populations (CD4, CD8, and CD4/CD8 cells) and B cells [Igh-6(-/-)] [6].
• To assess the importance of IgM domain assembly in B cell development we generated two transgenic mouse lines with truncated muH chains by homologous integration of the neomycin resistance gene (neo(r)) into exons C(mu)1 and C(mu)2 [19].
• However, Igh-6(-/-) mice, unlike Igh-6(+/+) C57BL/6 controls, did not survive an oral challenge with strain C5 at 4 months after vaccination [17].
• IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2-/-) knockout mice [20].
• Incorporation of D segments into IgH, TCRbeta, and TCRdelta chains also contributes to junctional diversification by substantially extending the length of the third CDR [21].

Regulatory relationships of Igh-6

• BSAP regulates transcription of several genes expressed in B cells and also the activity of the 3' IgH enhancer [22].
• To test this possibility, transgenic mice were generated that express Helios under the control of an Ig mu enhancer [23].
• To study the role of the murine heat-stable Ag (HSA) in lymphocyte maturation, we generated transgenic mice in which the HSA cDNA was under the transcriptional control of the TCR V beta promoter and Ig mu enhancer [24].

Other interactions of Igh-6

• These cells are B lineage precursors based on their capacity to generate B lineage cells rapidly in stromal-dependent culture and their expression of high levels of germline IgH transcripts in the absence of Rag-1/2 [25].
• The Igh-5 locus and the gene controlling the IgDI/IgDII ratio appear to map to the region between the Igh-6 and Igh-V loci [26].
• B-lymphocyte development in Pax-5-deficient mice becomes arrested at the transition of pre-B I to pre-B II cells i.e. at the stage when V(H) to D(H)J(H) rearrangements occur and when the pre-B-cell receptor, complete with muH chains and SL chains, is normally formed [27].
• Essential role of Stat5 for IL-5-dependent IgH switch recombination in mouse B cells [28].
• Absence of certain genes, such as CD40L, CD28, or Igh6, abrogated induction of autoimmunity [29].

Analytical, diagnostic and therapeutic context of Igh-6

• Allelic exclusion at the IgH locus was examined in B lineage cells of wild-type mice and mice unable to express the surrogate light chain molecule lambda 5 using a single-cell PCR approach [30].
• Fluorescent in situ hybridization analysis of primary splenic B cells isolated from normal and genetically manipulated mice showed that endogenous IgH, kappa and lambda alleles localized to different subnuclear environments after activation and had differential expression patterns [31].
• Genetic dissection of lupus pathogenesis: Sle3/5 impacts IgH CDR3 sequences, somatic mutations, and receptor editing [32].
• B lineage cell subpopulations were identified by double immunofluorescence assays using mAb of terminal deoxynucleotidyl transferase, 14.8 and cytoplasmic (cu) or surface (su) Ig mu-chains [33].
• In organ cultures of muH chain allotype heterozygous (muHa x muHb)F1 fetal livers a dose-dependent inhibition by allotype-specific monoclonal antibodies of sIgM+ immature B cells expressing the corresponding, but not the other, allotype was observed [34].

References