The BCR-SEQC initiative

Abstract

B cells express a diverse repertoire of antigen receptors known as B cell receptors (BCRs). BCR proteins are composed of two identical heavy chains (IGH) and two identical light chains (IGK or IGL). BCR diversity is generated by V(D)J recombination, assembling V, D and J gene segments for the heavy chain or V and J segments for the light chain. Further diversification occurs via nucleotide addition and deletion at junctions between the recombining gene segments. The third complementarity-determining region (CDR3) of IGH is the most diverse part of the BCR and serves as a clonal marker. After BCR assembly in the bone marrow, B cells migrate to peripheral lymphoid organs to participate in immune responses. Here, BCRs undergo further modification by somatic hypermutation (SHM) and class-switch recombination (for example, from IgM to IgG, IgA or IgE). These processes refine BCR specificity and function¹.

Adaptive immune receptor repertoire profiling (AIRR-seq) is performed by next-generation sequencing of BCR and T cell receptor (TCR) gene rearrangements². AIRR-seq can evaluate hundreds to billions of antigen receptors per individual. Profiling blood, bone marrow or lymph node samples can reveal B cell clones associated with responses to vaccines, self (autoimmunity), or sizable expansions linked to lymphoid malignancies. Longitudinal sampling further enables the study of clonal recruitment and intraclonal diversification in response to specific antigens.