Length diversity in CDR3 Domain of Immunoglobulin Kappa Chain during the Human Deelopment

Lee, Ji Soo; Lee, Soo Kon; Lee, Chan Hee; Song, Chang Ho

Abstract

The third complementarity determining region (CDR3) of the immunoglobulin (Ig) kappa () chain is known to be located at the center of antigen binding groove and critical for antibody specificity. Ig chain has been characterized by limited junctional diversity due to the absence of N-region addition resulting in relative conservation of CDR3 lengths with 9 or 10 amino acids. CDR3 region of 11 amino acids is only possible with N-region addition. Recently, x transcripts with 11 amino acids CDR3 was found to be expressed in normal individuals, and in autoimrnune disease such as rheumatoid arthritis, the fraction of 11 amino acids CDR3 of humkv325-derived chains was overexpressed compared to conventional adult peripheral B cells. However, the significance of this bias is difficult to interpret without a clear understanding of normal repertoire of CDR3 length during development. The purpose of this study is to determine whether developmental regulation of CDR3 amino acids codon lengths exists in chains expressed in the fetal liver, cord blood, and adult peripheral blood lymphocytes (PBL). Lymphocytes were seperated from fetal liver, cord blood and adult PBL and cDNA was generated from extracted mRNA. PCR-based CDR3 finger- printing assay was performed with VI-IV family specific primers. CDR3 length diversity of Ig x chain increases as the development proceeds. The length diversity most frequently occured in Vlll family derived transcripts including 11 amino acids CDR3. transcripts with 11 amino acids CDR3 were consitently expressed in both fetal and adult Ig repertoire. These results support the hypothesis that v chain CDR3 length is developmentally regulated and implicates the diversity of antigen-antibody specificity generation.