Functional antibodies exhibit light chain coherence

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• The adaptive immune system generates antibody diversity through V(D)J recombination.
• Antibodies consist of heavy and light chains, each with complementarity-determining regions (CDRs) crucial for antigen binding.
• Public clonotypes, B cells sharing identical heavy chains and CDRH3 sequences, are found across individuals.

Purpose of the Study:

• To investigate the association between heavy and light chain gene usage in public clonotypes.
• To determine if antibody functional status (naive vs. memory) influences light chain selection.
• To explore the implications of observed patterns for V(D)J recombination and immune selection.

Main Methods:

• Analysis of heavy and light chain gene usage in public clonotypes from different donors.
• Comparison of light chain gene usage probability between naive and memory B cell antibodies.
• Examination of heavy chain recurrence within individual donors.

Main Results:

• Naive antibodies show a low probability (~10%) of sharing the same light chain V gene within public clonotypes.
• Memory (functional) antibodies exhibit a high probability (~80%) of sharing the same light chain V gene, termed 'light chain coherence'.
• This coherence is also observed with recurrent similar heavy chains within a single donor.

Conclusions:

• The recurrence of naive antibodies appears stochastic, while functional antibodies show significant determinism.
• Light chain coherence in functional antibodies suggests a strong influence of the heavy chain on light chain selection.
• These findings highlight constraints and deterministic factors in V(D)J recombination and adaptive immune selection processes.