Generation of the primary antibody repertoire in rabbits: Expression of a diverse set of Igk-V genes may compensate for limited combinatorial diversity at the heavy chain locus

Devinder Sehgal, George Johnson, Tai T. Wu, Rose G. Mage*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

In mouse and human, generation of combinatorial diversity through use of different heavy and light chain variable region genes in immunoglobulin rearrangements can be a major contributor to the primary antibody repertoire. In rabbits, the contribution of the combinatorial mechanism to heavy chain diversity is minimal, as only a few Igh-V genes are rearranged and expressed. To investigate the contribution of combinatorial diversity toward generation of the rabbit V(κ) repertoire, we constructed five genomic libraries from rabbit kidney DNA and 1 cDNA library from the bone marrow of a 1-day-old rabbit using a series of polymerase chain reaction-based strategies. Our analyses indicate that most of the sequences that we recovered from our libraries belong to a single family and some are extremely similar. The actual number of germline Igk-V genes is potentially greater than our conservative estimate of at least 39, 28 of which we found expressed as mRNA. The germline Igk-V genes display different lengths of the coding region 3' of Cys 88 ranging from 7 to 12 amino acids, resulting in CDR3 length heterogeneity among functional V(κ)J(κ) sequences ranging from 8 to 15 amino acids. Some of the V(κ)J(κ) junctions had N and P nucleotide additions. Thus, in contrast to limited combinatorial diversity of its heavy chain, the rabbit can draw upon a diverse set of germline Igk-V genes. The κ light chain has the potential to be a major contributor toward generation of the antibody specificities of the rabbit pre-immune repertoire.

Original languageEnglish (US)
Pages (from-to)31-42
Number of pages12
JournalImmunogenetics
Volume50
Issue number1-2
DOIs
StatePublished - Oct 25 1999

Keywords

  • Combinatorial diversity
  • Expressed Igk-V genes
  • Germline Igk-V genes
  • IGVK families
  • Rabbit

ASJC Scopus subject areas

  • Immunology
  • Genetics

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