Enlightening Human B-Cell Diversity

Since their discovery in the 60s´, B cells have been extensively studied because of their unique and critical role in immunoglobulin (Ig) production. In addition, B cells contribute to other aspects of the immune response via antigen presentation to T cells and cytokine production. Despite the intensive study of B cells, its classification in different subsets based on surface markers remained controversial. Historically, B cells in the periphery (i.e., blood, secondary lymphoid organs) were classified according to their maturation stage and the Ig isotype expressed in 5 populations: transitional, naive, non-switched memory, switched memory and plasma cells. Importantly, this classification does not reflect precisely functional aspects (i.e., metabolism, cell signaling, tissue of origin), and in some cases the markers used to identify B-cell subsets were faulty. For example, CD27 was long considered a classical marker of memory B cells and associated with somatic hypermutation (SHM), however some memory B cells lack CD27 expression. In this context, B-cell biologists were demanding to update the criteria used to classify B cells and the inclusion of novel functionality markers, which has been possible with the advent of single cell multi-omics.