Germ line basis for antibody diversity

Area of Science:

• Immunogenetics
• Molecular Biology
• Genomics

Background:

• Antibody polypeptide chains are formed by gene pairs: one constant (C) gene and one variable (V) gene.
• Previous research suggested a single C gene copy per haploid genome and multiple V genes for antibody diversity.

Purpose of the Study:

• To investigate the gene copy number for immunoglobulin heavy chains (mRNA-H).
• To confirm the existence of single C genes and multiple V genes in the antibody gene repertoire.

Main Methods:

• Hybridization of purified mRNA coding for immunoglobulin heavy chain (mRNA-H) with excess DNA.
• Isolation of mRNA-H and its nuclear precursor using specific immunoglobulin interaction.

Main Results:

• Hybridization results confirm the presence of a single C gene and multiple V genes for immunoglobulin heavy chains.
• The estimated number of V genes is approximately 10^4, indicating significant V gene redundancy.
• A nuclear precursor of mRNA-H was identified, supporting direct V-C gene joining before transcription.

Conclusions:

• The antibody gene structure involves a single C gene paired with one of many V genes.
• Significant V gene redundancy, maintained by expansion and contraction, is essential for generating antibody diversity.
• Evidence supports the direct joining of V and C genes at the DNA level prior to transcription.