Antigen nature and complexity influence human antibody light chain usage and specificity

Area of Science:

• Immunology
• Molecular Biology

Background:

• Human antibodies are composed of heavy chains and either kappa (κ) or lambda (λ) light chains.
• The differential roles of kappa and lambda light chains in antibody responses are not fully understood.

Purpose of the Study:

• To investigate how kappa and lambda light chains influence human antibody responses to polysaccharide and protein antigens.
• To analyze light chain usage in monoclonal antibodies and serum following vaccination.

Main Methods:

• Analysis of human monoclonal antibodies from antibody-secreting cells after Pneumovax23 vaccination.
• Quantification of kappa and lambda light chain usage in serum antibodies against various antigens, including pneumococcal serotypes, CRM197, EBNA-1, and influenza strains.

Main Results:

• Antibody responses to cell wall polysaccharides were predominantly kappa.
• Certain pneumococcal serotypes showed preferential light chain usage (e.g., lambda for 14 and 19A, kappa for 6A and 23F).
• Responses to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1 were largely kappa-dominant, while influenza vaccine responses were more balanced.

Conclusions:

• Antigens with limited epitopes tend to elicit antibody responses with restricted light chain usage.
• Lambda light chains provide specificities that are distinct from and complementary to those of kappa light chains, contributing to a comprehensive immune repertoire.