Overusage of mouse DH gene segment, DFL16.1, is strain-dependent and determined by cis-acting elements

Abstract

The DJH structure is of particular importance for diversity in the immunoglobulin heavy chain because it encodes most of CDR3. Here, we investigate mechanisms responsible for generating the DJH structure. We found DFL16.1 was used at a high frequency in normal and transformed pre-B cells (fetal liver > 50%, A-MuLV lines approximately equal to 25%). One DFL16.1JH1 structure was found repeatedly and was also present in DJH and VDJH databases, suggesting this structure may be conserved in the primary repertoire. Genetic analysis demonstrated that C57BL/6 mice use DFL16.1 in DJH structures more frequently than BALB/c. Examination of individual alleles in (C57BL/6 x BALB/c)F1 A-MuLV cell lines revealed that the C57BL/6-derived allele used DFL16.1 twice as often as the BALB/c. This result indicates that part of the mechanism ensuring overusage of DFL16.1 gene segments is cis-acting.