Immunoglobulin Genes

Abstract

Through a process of random gene segment rearrangements and mutation, the immune system is uniquely positioned to generate an apparently inexhaustible array of responses to foreign antigenic challenges.

Keywords: immunoglobulin; class‐switching; V(D); rearrangement; repertoire

Figure 1.

Recognition signal sequence for DH to JH and VH to DHJH rearrangement. The recombination recognition sequence contains two conserved DNA sequences, a heptamer, which is essentially palindromic (CACAGTG), and a nonamer (GGTTTTTGT); these are separated by spacer DNA of either 23 bp (not shown) or 12 bp (shown).

Figure 2.

H‐chain locus, showing the organization of a portion of the constant gene (CH) segments. Class switching is mediated by a DNA rearrangement event called switch recombination (S–S recombination). In vivo studies have shown that S–S recombination occurs between switch (S) regions in the 5′ flanking sequences of the Cμ gene (i.e. Sμ), and in the 5′ flanking sequences of the genes of other constant regions (e.g. Sγ3), except for Cδ. Structural studies have shown that S regions are composed of tandemly repeated short DNA sequences that vary in sequence similarity between different constant gene segments.

Figure 3.

Deletion model of class switch recombination. The genomic organization prior to recombination consists of a rearranged V(D)J region, which is 5′ of the Sμ–Cμ gene segment. Downstream of the Cμ gene segment are the constant region gene segments. All constant region genes have a 5′ switch or S region. The organization of the genome is such that antibodies of class M are produced first. The orchestration of the recombination between two S regions involves the juxtaposition of two S regions. Through a process of DNA recombination the two S regions are recombined. The intervening DNA is removed from the genome as a closed circle. This recombination has the effect of deleting the Cμ constant region gene and the remnants of the S region from both the incoming constant region gene and the outgoing C region gene. The end result of this recombination is that the incoming constant region gene, Cγ2b, is placed downstream of the V(D)J genes. The newly organized genome now produces antibodies of class Cγ2b.

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Web Links

B‐cell CLL/lymphoma 2 (BCL2); LocusID: 596. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=596

Recombination activation gene 1 (RAG1); LocusID: 5896. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5896

Recombination activation gene 2 (RAG2); LocusID: 5897. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5897

B‐cell CLL/lymphoma 2 (BCL2); MIM number: 151430. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?151430

Recombination activation gene 1 (RAG1); MIM number: 179615. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?179615

Recombination activation gene 2 (RAG2); MIM number: 179616. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?179616

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How to Cite close
Fanning, Liam J(Jan 2006) Immunoglobulin Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005668]