Nucleotide sequence of immunoglobulin heavy chain joining segments between translocated VH and mu constant regions genes.

Abstract

To investigate the mechanism of recombination of immunoglobulin [Ig[H chain variable (V) constant (C) region genes, the authors determined the nucleotide sequence of a large portion of the recombination region between an active C.mu. gene and its associated VH gene, isolated from an IgM-secreting mouse plasmacytoma, HPC76. By comparison with the sequence of the .mu. mRNA, the exact boundaries of the intervening sequence between the VH76 and C.mu. genes was determined. The rearranged VH76 gene encodes up to amino acid 116 without interruption, the 3''99 nucleotides (the JH76 joining region) being derived from an embryonic JH segment (JH315) whose sequence was recently determined [Early et al., 1980). The active JH76 does not use the 1st 2 codons of the embryonic JH315 from which it is derived. This indicates that V-J recombination is important in generating diversity within the 3rd hypervariable region of H chains. Another JH segment, (JHA4), located 336 nucleotides 3'' to the rearranged JH76 segment, was identified. This JH segment is expressed in the H chains of anti-levan myeloma proteins, which have truncated 3rd hypervariable regions. The nucleotide sequence 5'' to JHA4 is important for generating V region genes with shortened 3rd hypervariable regions.