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

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The diversity (DJH) structure is crucial for immunoglobulin heavy chain diversity, encoding the majority of CDR3.
• Understanding the mechanisms generating DJH structures is key to comprehending immune system development and diversity.

Purpose of the Study:

• To investigate the mechanisms responsible for generating the DJH structure.
• To identify specific gene segments involved in DJH formation and their usage frequency.

Main Methods:

• Analysis of DFL16.1 gene segment usage in normal and transformed pre-B cells.
• Comparison of DJH structure usage between C57BL/6 and BALB/c mouse strains.
• Examination of DJH structure formation in F1 hybrid cell lines to assess allelic contributions.

Main Results:

• DFL16.1 is frequently used in DJH structures in both normal (fetal liver >50%) and transformed (A-MuLV lines ~25%) pre-B cells.
• A specific DFL16.1JH1 structure was repeatedly observed and found in DJH and VDJH databases, suggesting conservation.
• C57BL/6 mice exhibit higher DFL16.1 usage in DJH structures compared to BALB/c mice, with a cis-acting mechanism identified.

Conclusions:

• DFL16.1 is a significantly utilized gene segment in DJH structure formation.
• The overusage of DFL16.1 gene segments in DJH structures is partly regulated by cis-acting elements.
• Findings suggest a conserved mechanism in the primary immunoglobulin repertoire formation.