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 language | English (US) |
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Pages (from-to) | 31-42 |
Number of pages | 12 |
Journal | Immunogenetics |
Volume | 50 |
Issue number | 1-2 |
DOIs | |
State | Published - 1999 |
Keywords
- Combinatorial diversity
- Expressed Igk-V genes
- Germline Igk-V genes
- IGVK families
- Rabbit
ASJC Scopus subject areas
- Immunology
- Genetics