Allotype and charge-related differences in the immune response

Area of Science:

• Immunogenetics
• Molecular immunology
• Allotype expression

Background:

• The Ab kappa light chain locus in rabbits exhibits allotypic polymorphism, with Ab4 and Ab9 being common allotypes.
• Antibody production is influenced by genetic factors, including immunoglobulin allotypes.

Purpose of the Study:

• To investigate the influence of rabbit immunoglobulin allotypes (Ab4 and Ab9) on antibody production against antigens of varying electric charges.
• To determine if allotypic differences in antibody charge correlate with quantitative differences in antibody response.

Main Methods:

• Immunization of homozygous Ab4/Ab4 and Ab9/Ab9 rabbits with negatively charged antigens (BSA, OV, TG, (TG)--AL) and a positively charged antigen (lysozyme).
• Assessment of antibody relative electric charges using Sephadex A-50 chromatography.
• Analysis of antibody charge distribution and average electric charge.

Main Results:

• Homozygous Ab9 rabbits produced less antibody than Ab4 homozygotes when immunized with negatively charged antigens.
• Both Ab4 and Ab9 rabbits showed similar antibody responses to the positively charged antigen, lysozyme.
• Antibody charge distribution depended on the eliciting antigen's charge; Ab9 antibodies were less positively charged than Ab4 antibodies.

Conclusions:

• Differences in average electric charges and charge range between Ig Ab4 and Ig Ab9 antibodies explain quantitative antibody production differences against negatively charged antigens.
• Allotypic variations in antibody charge may contribute to the unequal phenotypic expression of light chain genes observed in Ab4/Ab9 heterozygotes.