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Circulating B Cell Antibody Repertoire in Healthy Individuals is Highly Diverse, Study Reveals

NEW YORK (GenomeWeb) – A team led by researchers at the Scripps Research Institute has characterized baseline human antibody collections in 10 healthy adults and found both diversity and universality in the adaptive immune receptor sequences circulating in the blood.

The researchers profiled antibody genes in circulating B cells, or B lymphocytes, from half a dozen blood samples apiece from the participants in an effort to understand the repertoire of antibodies these cells secretes. Their results, appearing online yesterday in Nature, revealed nearly three billion distinct antibody heavy-chain sequences that reflected extreme antibody diversity as well as subsets of common antibody clonotypes.

"This dataset enables genetic study of the baseline human antibody repertoire at an unprecedented depth and granularity, which reveals largely unique repertoires for each individual studied, a sub-population of universally shared antibody clonotypes, and an exceptional overall diversity of the antibody repertoire," co-corresponding and senior author Dennis Burton, an immunology and microbiology researcher affiliated with Scripps, the Ragon Institute, and the Human Vaccines Project, and his colleagues wrote.

"Although it is known that convergent antibodies may arise from different individuals in response to immunological exposure … the overall prevalence of repertoire sharing is unknown," the authors explained.

The team used quantitative PCR and sequencing to quantify and assess antibody gene amplicons in 18 libraries apiece for 10 individuals of self-reported African American or Caucasian ancestry between the ages of 18 and 30. Starting with total RNA, they used reverse transcription and PCR amplification on antibody genes in triplicate from six samples per person.

"To estimate repertoire diversity and minimize the effects of sequencing and amplification error, we first considered clonotype diversity," the authors noted, explaining that each clonotype "is a collection of sequences using the same V and J genes, and encoding an identical CDRH3 amino acid sequence."

Along with antibody clonotypes shared between two or more of the individuals, the team used two computational tools to estimate the broader antibody diversity within the 10 study participants, uncovering vast numbers of unique heavy-chain antibody sequences.

The authors cautioned that the current findings reflect only the B cells in the blood of a small set of individuals from a specific age span and geographic area, neglecting the B lymphocytes found in other organs or in individuals from other geographic or ethnic backgrounds.

Even so, they noted that the results point to the possibility of tapping into adaptive immune receptor sequences to retrace prior infections, diagnose infections, or develop antibody repertoire sequence-informed treatments. 

"[T]he individuality of the baseline repertoire of each subject suggests that the personalization of vaccine delivery and therapeutic intervention may produce substantial benefits in the treatment and prevention of infectious diseases," they concluded.