Transcriptional enhancers of immunoglobulin light chain genes in Atlantic cod ( Gadus morhua )

We have characterized the genomic organization of the three zebrafish L chain isotypes and found they all differed from those reported in other teleost fishes. Two of the zebrafish L chain isotypes are encoded by two loci, each carrying multiple V gene segments. To understand the derivation of these L chain genes and their organizations, we performed phylogenetic analyses and show that IgL organization can diverge considerably among closely related species. Except in zebrafish, the teleost fish IgL each contain only two to four recombinogenic components (one to three V, one J) and exist in multiple copies. BCR heterogeneity can be generated, but this arrangement apparently provides neither combinatorial diversification nor an opportunity for the secondary rearrangements that, in mammals, take place during receptor editing, a process crucial to the promotion of tolerance in developing lymphocytes. Examination of the zebrafish IgL recombination possibilities gave insight into how the suppression of self-reactivity by receptor editing might be managed, including in miniloci. We suggest that, despite the diverse IgL organizations in early and higher vertebrates, two elements essential to generating the Ab repertoire are retained: the numerous genes/loci for ligand-binding diversification and the potential for correcting unwanted specificities that arise.

Section: Evolution Of Igl Gene Organizationmentioning

confidence: 99%

Section: Why More Than One L Chain Locus?mentioning

confidence: 99%

Section: Why More Than One L Chain Locus?mentioning

confidence: 99%

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Diverse Immunoglobulin Light Chain Organizations in Fish Retain Potential to Revise B Cell Receptor Specificities

Hsu

Criscitiello

2006

“…This fragment contains seven octamer motifs and two E5 motifs that match those in the previously described catfish E 3Ј enhancer (11). Plasmid pCMV-LUC served as an internal control for transfection efficiencies (21). Plasmid DNAs were purified using QiaFilter Plasmid Maxi kit (Qiagen, Valencia, CA).…”

Section: Plasmids Transient Transfections and Reporter Assaysmentioning

confidence: 99%

TheIgHLocus of the Channel Catfish,Ictalurus punctatus, Contains Multiple Constant Region Gene Sequences: Different Genes Encode Heavy Chains of Membrane and Secreted IgD

Bengtén

Quiniou

Stuge

et al. 2002

Self Cite

122

The δ-chain of catfish IgD was initially characterized as a unique chimeric molecule containing a rearranged VDJ spliced to Cμ1, seven C domain-encoding exons (δ1–δ7), and a transmembrane tail. The presence of cDNA forms showing splicing of δ7 to an exon encoding a secretory tail was interpreted to indicate that membrane (δm) and secreted (δs) forms were likely expressed from a single gene by alternative RNA processing. Subsequent cloning and sequence analyses have unexpectedly revealed the presence of three δ C region genes, each linked to a μ gene or pseudogene. The first (IGHD1) is located 1.6 kb 3′ of the functional Cμ (IGHM1). The second (IGHD3) is positioned immediately downstream of a pseudo Cμ (IGHM3P), ∼725 kb 5′ of IGHM1. These two δ genes are highly similar in sequence and each contains a tandem duplication of δ2-δ3-δ4. However, IGHD1 has a terminal exon encoding the transmembrane region, whereas IGHD3 has a single terminal exon encoding a secreted tail. The occurrence of IGHD3 immediately downstream of a μ pseudogene indicates that the putative δs product may not be expressed as a chimeric μδ molecule. Western blots and protein sequencing data indicate that an IGHD3-encoded protein is expressed in catfish serum. Thus, catfish δm transcripts appear to originate from IGHD1, whereas δs transcripts originate from IGHD3 rather than, as previously inferred, from a single expressed δ gene. The third δ (IGHD2) is associated with a pseudo Cμ (IGHM2P); its presence is inferred by Southern blot analyses.

“…Moreover, in two Xenopus species there is a possibility for gene inactivation in that the 39-most Jk is a pseudogene, to which rearrangements have in fact been recovered (20). In bony fish, the IgL are organized as many small loci, each with varying small numbers of V, J, and C exons, some of which share enhancers (15,21). The tandem positioning of gene segments and the proximity of many loci offer the potential for removing unwanted VJ rearrangements (22).…”

mentioning

confidence: 99%

Evidence for Ig Light Chain Isotype Exclusion in Shark B Lymphocytes Suggests Ordered Mechanisms

Iacoangeli

Lui

Haines

et al. 2017

Unlike most vertebrates, the shark IgL gene organization precludes secondary rearrangements that delete self-reactive VJ rearranged genes. Nurse sharks express four L chain isotypes, κ, λ, σ, and σ-2, encoded by 35 functional minigenes or clusters. The sequence of gene activation/expression and receptor editing of these isotypes have not been studied. We therefore investigated the extent of isotypic exclusion in separated B cell subpopulations. Surface Ig (sIg)κ–expressing cells, isolated with mAb LK14 that recognizes Cκ, carry predominantly nonproductive rearrangements of other L chain isotypes. Conversely, after depletion with LK14, sIgM+ cells contained largely nonproductive κ and enrichment for in-frame VJ of the others. Because some isotypic inclusion was observed at the mRNA level, expression in the BCR was examined. Functional λ mRNA was obtained, as expected, from the LK14-depleted population, but was also in sIgκ+ splenocytes. Whereas λ somatic mutants from the depleted sample displayed evidence of positive selection, the λ genes in sIgκ+ cells accumulated bystander mutations indicating a failure to express their products at the cell surface in association with the BCR H chain. In conclusion, a shark B cell expresses one L chain isotype at the surface and other isotypes as nonproductive VJ, sterile transcripts, or in-frame VJ whose products may not associate with the H chain. Based on the mRNA content found in the B cell subpopulations, an order of L chain gene activation is suggested as: σ-2 followed by κ, then σ and λ.