Hiding in plain sight: time to unlock autoimmune clues in human CD5+ B cells by using nextgen technology.

CD5+ B cells expand in many autoimmune diseases, including type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Furthermore, CD5+ B cells contain important subsets: IL-10-producing B-reg cells, FasL-expressing subset, and the majority of pre-naive B cells. In addition, they are major sources of natural autoantibodies, which are polyreactive and autoreactive. Thus, CD5+ B cells are clearly loaded with autoimmune clues that are yet to be unlocked and understood. We hypothesize that human CD5+ B cells are likely to yield enormously important novel information about the role of B cells in autoimmune disease if analyzed using the new technological advances in molecular biology and genomics. Use of high-throughput sequencing of B cell receptors (BCR) of CD5+ B cells could reveal public BCRs associated with autoimmune diseases, whereas transcriptional analysis of CD5+ B cells using single-cell RNA-seq may delineate distinct sublineages and their relationship to conventional B cells. If it turns out that autoimmune repertoires are concentrated in CD5+ B cells, given that CD5+ B cells are clearly identifiable by flow cytometry, therapeutic strategies can be developed to safely remove CD5+ B cells to mitigate ongoing autoimmunity and protect at-risk individuals.