Assessing human B cell repertoire diversity and convergence

Abstract

A hallmark of the adaptive immune system is the specificity of B cell and T cell responses. Mechanistically, this feature relies on the fact that the two genes that encode B cell and T cell antigen receptors are not germline encoded and instead are assembled from a large number of small gene segments during lymphocyte development. The underlying somatic gene recombination process can generate a quasi-unlimited repertoire of antigen receptors. The high degree of diversity is essential to guarantee recognition of nearly any antigenic structure to protect from the large variety of potential invading pathogens and to keep the balance with commensals. Due to the enormous complexity of the antigen receptor repertoire, our understanding of its actual size and functional convergence at the level of the individual and the population is still limited. A better understanding of the actual degree of diversity could help to predict adaptive immune responses and would have wide implications for the development of preventive and therapeutic measures against infectious and autoimmune diseases as well as cancer. Here, we discuss the recent advances in the field with a specific focus on B cells and the function of antibodies.

Functional Enrichment and Analysis of Antigen-Specific Memory B Cell Antibody Repertoires in PBMCs

“…Clonal expansions of B cells occur in response to specific immune stimulation and evidence for a corresponding convergence of germline gene arrangements has been shown [e.g., (23–27)]. Clonal families represent in vivo antibody molecular evolution to a consensus directed against common epitopes of vaccines or disease.…”

Breaking the law: unconventional strategies for antibody diversification

“…Antibodies first appeared in evolution in cartilaginous fishes more than 500 million years ago 1 Theoretically, under physiological conditions the human immune system can generate BCRs with 10 26 distinct sequences 3,4 , an astronomical number that is far greater than the calculated number of all B cell clones that can be generated during the lifespan of a healthy human (estimated to be 4 × 10 14 ) 3 . The recent advent of technologies that allow highthroughput sequencing of the entire human B cell repertoire 5,6 as well as isolation and characterization of human monoclonal antibodies 7 , 8 has contributed to the identification and better characterization of some alternative or 'unconventional' mechanisms that contribute to diversification of the antibody repertoire. For example, antibodies have been reported to integrate non-immunoglobulin proteins as part of their binding sites and use these proteins for specific binding to target antigens.…”

Functional Enrichment and Analysis of Antigen-Specific Memory B Cell Antibody Repertoires in PBMCs

“…Clonal expansions of B cells occur in response to specific immune stimulation and evidence for a corresponding convergence of germline gene arrangements has been shown (e.g. Briney B. et al 2019, Setliff, I. et al 2018, Imkeller, K.,and Wardemann, H. 2018. Clonal families represent in vivo antibody molecular evolution to a consensus directed against common epitopes of vaccines or disease.…”