Double‐negative (DN) B cells: an under‐recognized effector memory B cell subset in autoimmunity

Summary Human B cells could be divided into four classical subsets based on CD27 and immunoglobulin (Ig)D expression. Distinct from the other three well‐studied subsets, CD27−IgD− B cells, also termed as double‐negative (DN) B cells, have long been neglected. However, in recent years emerging evidence shows that DN B cells are unique memory B cells with important functions. They are expanded in a variety of diseases, especially in autoimmune diseases, contributing to the disease pathogenesis. Here, we briefly review the studies on DN B cells, including their origins, characteristics, subsets and roles in diseases, to try to bring new insights into this under‐recognized B cell subset. Double‐negative (CD27‐IgD‐, DN) B cells are unique memory B cells with more diversified population. Three models have been proposed about the origins of DN B cells. DN B cells are expanded in various diseases and could differentiate into plasma cells and facilitate immune responses, potentially contributing to the pathogenesis of autoimmune diseases.