제목 : Deciphering Human B cell Receptor Repertoires: What Have We Learned?

내용 : B cells recognize antigens via membrane-expressed B-cell receptors (BCR). BCR is the hetero-tetrameric complex of heavy and light chain polypeptides and the heavy chain plays major role in antigen binding. With the combination of VH, DH and JH genes, the heavy chain can achieve the theoretical complexity of 1 X 10E12. A high-throughput genomic analysis of BCR heavy chain likewise estimated a complexity of 3.5 X 10E11. Meanwhile, the number of B cells in humans at any moment does not exceed 1 X 10E11 and the number of B cell clone defined by unique BCR sequence is even smaller. Therefore, individual human-beings are destined to harbor only a fraction of theoretically achievable BCR repertoire. The mechanism shaping the BCR repertoire in each person is yet to be clarified but would be influenced by environmental factors like microbiome, viruses, etc. In accordance with this assumption, humans share common clonotypes with much higher frequency than mathematically calculated. Several groups, including ours, have already shown that stereotypic VH clonotypes exist among SARS-CoV-2 or HIV infected patients and several autoimmune diseases. We believe that in silico reconstitution of BCR repertoires and identification of stereotypical BCR sequences related to human pathology have diagnostic potential. Furthermore, monitoring changes of clinically significant BCR sequences and isotype conversion would provide prognostic clues.