Disease relevance of Igll1

• Comparison of the nucleotide sequence of a 1 kb cDNA clone with the sequence of a genomic clone isolated from 70Z/3 murine pre-B lymphoma cells shows lambda 5 is composed of three exons spanning a 3.75 kb DNA segment [1].
• Fusion of plasmacytoma cells with normal pre B cells to generate pre B hybridomas leads to down-regulation of VpreB/lambda 5 expression.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
• A common variable immunodeficiency (CVID) patient, who carries mutations on both alleles of the gene encoding the surrogate light chain component lambda 5/14.1, shows a similar phenotype of B-cell deficiency as the lambda 5-deficient mutant mouse [3].
• Pre-B-cell development in the absence of lambda 5 in transgenic mice expressing a heavy-chain disease protein [4].

High impact information on Igll1

• Primarily, these mice have few B220+ IgM+ mature B or B220+ CD43- pre-B cells in the bone marrow, reduced frequencies of V(D)J and V kappa J kappa recombination of the immunoglobulin loci, and lower expression levels of the immunoglobulin, RAG-1, RAG-2, and lambda 5 genes [5].
• The expression of Vpre-B/lambda 5 surrogate light chain in early bone marrow precursor B cells of normal and B cell-deficient mutant mice [6].
• A critical role of lambda 5 protein in B cell development [7].
• We have generated mice in which the lambda 5 gene is inactivated by targeted gene disruption in embryonic stem cells [7].
• Our findings define a new immunoglobulin L-chain-related locus, which we call lambda 5, that is selectively transcribed in pre-B lymphocytes [8].

Biological context of Igll1

• We have now found, 4.6 kb upstream of lambda 5, another gene composed of two exons which is selectively expressed in pre-B cell lines as a 0.85 kb mRNA potentially coding for a protein of 142 amino acids including a 19 amino acid-long signal peptide [9].
• Transgenic human lambda 5 rescues the murine lambda 5 nullizygous phenotype [10].
• High levels of expression of the transgenic hu lambda 5 gene were detected in bone marrow pro-B and pre-B cells at the mRNA and protein levels, suggesting that the 28-kb transgene fragment contains all the transcriptional elements necessary for the stage-specific B progenitor expression of hu lambda 5 [10].
• A gene encoding the lambda 5 light chain constant region was isolated from a genomic library from the SPE mouse strain (C lambda 5S) [11].
• The data indicate that the elements responsible for the enhancer activity (-210 to -22) are part of the lambda 5 gene promoter and likely confer the tissue and stage specificity via positive elements within the -210 to -22 region [12].

Anatomical context of Igll1

• The murine gene lambda 5 is selectively expressed in pre-B lymphocytes [9].
• These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either lambda 5 or VpreB1/VpreB2 [13].
• The VpreB2 gene is functional, as it directed the production in COS cells of a 16-kDa protein that assembled with lambda 5 and was recognized by a VpreB-specific monoclonal antibody [14].
• They also down-regulate the expression of VpreB and lambda 5, and lose the capacity to proliferate on stromal cells in the presence of IL-7 [15].
• The chromosomal location of the murine lambda 5 gene was analyzed by Southern hybridization using restriction enzyme-digested DNA from a panel of 15 mouse X hamster somatic cell hybrids [16].

Associations of Igll1 with chemical compounds

• Interaction of murine precursor B cell receptor with stroma cells is controlled by the unique tail of lambda 5 and stroma cell-associated heparan sulfate [17].
• Lipopolysaccharide (LPS) stimulation of 70Z/3 pre B cells does not turn off lambda 5 expression [2].
• Culturing NFS-5.3 with heparin similarly decreases the membrane-form mu; however, it increases the surface level of a pentameric mu molecule containing secreted-form mu (microS) heavy chains, disulfide-linked omega (lambda 5) chains, and noncovalently associated proteins [18].
• In the presence of a heterologous enhancer, 5' lambda 5 confers pre-B cell-specific expression on the reporter gene chloramphenicol acetyl-transferase [19].

Physical interactions of Igll1

• A complex of glycoproteins is associated with VpreB/lambda 5 surrogate light chain on the surface of mu heavy chain-negative early precursor B cell lines [20].

Regulatory relationships of Igll1

• The VpreB1 protein is thought to be expressed on the surface of pre-B cells in association with lambda 5 and mu heavy chain, and to play an important role on B cell differentiation [21].
• The lambda 5 protein is expressed in pre-B cells in association with VpreB and mu-heavy chains, and is critical for differentiation to the B cell stage [12].
• Bone marrow cells from immunoglobulin HC transgenic RAG-2-/- mice have up-regulated expression of germ-line kappa LC gene transcripts and down-regulated expression of lambda 5 surrogate LCs (SLCs) [22].
• The c-myc protein represses the lambda 5 and TdT initiators [23].

Other interactions of Igll1

• The putative protein encoded by VpreB is a potential candidate for association with the putative protein encoded by lambda 5, and thereby a candidate for association with H chains in pre-B cells [9].
• Therefore, we conclude that the hu lambda 5 polypeptide can biochemically and functionally substitute for m lambda 5 in vivo in pre-B lymphocyte differentiation and proliferation [10].
• R-PCR also demonstrates expression of lambda 5, RAG-1 and RAG-2, which are specifically associated with pre-B stage lymphocytes [24].
• Starting B-cell lymphopoiesis (9-12 days pc) is characterized by nonexpression of the surrogate light chain lambda 5-encoding gene and biased usage of IgH DJ4 rearrangements [25].
• Lambda5 is required for rearrangement of the Ig kappa light chain gene in pro-B cell lines [26].

Analytical, diagnostic and therapeutic context of Igll1

• The conservation of the C lambda 5 gene in various Mus species was observed by high stringency Southern blot analyses using a C lambda 5S probe on DNA sample from members of four different groups of wild mice [11].
• 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 [27].
• Using this system and employing mutant mice in which the membrane exon of the mu chain, the lambda 5 gene, or the JH locus was inactivated by gene targeting, we found that expression of the pre-B cell receptor complex is necessary for the transition from the large CD43+ to the small CD43- pre-B cell stage [28].

References