1 | AGE-ASSOCIATED B CELLS
Age-associated B cells (ABCs) constitute a CD11c+ T-bet+ B-cell population that expands continuously with age in healthy individuals,1 but also displays a premature accumulation in cases of autoimmune and/or infectious diseases.2-5 In autoimmune settings, ABCs are implicated in the production of autoreactive immunoglobulin G,2 the enhanced antigen presentation to T cells, and the formation of spontaneous germinal centers.6,7 T-bet, which is a transcription factor highly expressed in ABCs, is considered to be the master regulator of all these processes,8 although new data suggest that its expression may not be required for the generation of functional ABCs.9
In humans, the ABC subset is also known as double-negative (DN) B cells because of the lack of immunoglobulin D and CD27 memory marker expression.10-12 DN B cells have been further divided into two subgroups, based on the expression of the follicular homing marker CXCR5.13 More specifically, the CXCR5+ cells (DN1) are expanded in elderly healthy individuals and lack T-bet expression, whereas the CXCR5–cells (DN2) express T-bet and are more marked in autoimmune diseases (mostly systemic lupus erythematosus).10,11,13 The DN2 cells are hyperresponsive to Toll-like receptor 7 (TLR7) signaling, so are poised to generate autoreactive antibody-secreting plasmablasts.13 In general though, their role in the development of autoimmunity remains elusive.