Functions of double-negative B cells in autoimmune diseases, infections, and cancers.

Most mature B cells can be divided into four subtypes based on the expression of the surface markers IgD and CD27: IgD + CD27 - naïve B cells, IgD + CD27 + unswitched memory B cells, IgD - CD27 + switched memory B cells, and IgD - CD27 - double-negative (DN) B cells. Despite their small population size in normal peripheral blood, DN B cells play integral roles in various diseases. For example, they generate autoimmunity in autoimmune conditions, while these cells may generate both autoimmune and antipathogenic responses in COVID-19, or act in a purely antipathogenic capacity in malaria. Recently, DN B cells have been identified in nasopharyngeal carcinoma and non-small-cell lung cancers, where they may play an immunosuppressive role. The distinct functions that DN B cells play in different diseases suggest that they are a heterogeneous B-cell population. Therefore, further study of the mechanisms underlying the involvement of DN B cells in these diseases is essential for understanding their pathogenesis and the development of therapeutic strategies. Further research is thus warranted to characterize the DN B-cell population in detail.