Comparison of the immunoglobulin heavy-chain complementarity determining region-3 structure among the DNA sequences...

To study the recombinational significance of the (immunoglobulin heavy) IgH chain gene in human B-cell development, we compared the complementarity determining region (CDR)-3 sequences of the DNA and the mu-transcripts from human normal pre-B cells and mature B cells, and the gamma-transcripts from bone marrow cells. The CDR-3 sequences were longer in the DNA than in the mu- and gamma-transcripts, and this was independent of whether or not the rearrangement was productive. The DLR family genes were less frequently used in the mu- and gamma-transcripts. When translated into amino acids, all CDR-3 sequences from the mu- and gamma-transcripts were productive, although 26.2% of the DNA sequences had stop codons in the D element and/or frameshifts of the JH gene segments. The CDR-3 of the productive DNA sequences in pre-B cells frequently (26.6%) contained at least three continuous hydrophobic amino acids, which were mainly coded by the DLR and DXP family genes at the third reading frame. However, such motifs were rate in the mu-transcripts of pre-B (7.7%) and mature B cells (3.9%), and in the gamma-transcripts of bone marrow cells (1.1%) as well as in the DNA of mature B cells (10.4%). These findings suggested that the length and/or hydrophobicity of the IgH CDR-3 might play a role in the selection mechanisms of B-cell development.