Key words Rabbit
Germline Igk-V genes
Expressed Igk-V genes
Springer Online Journal Archives 1860-2000
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 Vκ 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 VκJκ sequences ranging from 8 to 15 amino acids. Some of the VκJκ 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.
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