Background Age-associated B cells (ABCs) are a particular population of B cells that CD11c and T-bet double positive, rarely observed in healthy young individuals. These atypical B cells are from an extrafollicular (EF) response, unlike T cell-dependent germinal center (GC) response that produces long-lived, high-affinity antibody-secreting B cells. Since ABCs not going through GC response, somatic hypermutation or class-switching poorly happens, and they secrete pathogenic autoantibodies. ABCs expansion and chronic autoimmune disease correlation are well-established, especially in systemic lupus erythematosus (SLE). Some individuals with active SLE display abnormal expansion of ABCs regardless of age, but how ABCs impact the disease remains unclear. Not just aged or autoimmune disease individuals, the infectious condition could increase the ABCs differentiation. In such case, IL-21 drives extrafollicular CD11c+ B cells. It means IL-21, which plays a multifunctional role in B cell differentiation, could influence the expansion of ABCs also in aged and autoimmune diseases. Therefore, we experimented to confirm whether ABCs can express autoimmune disease phenotypes and whether IL-21 is related with ABCs.

Methods We inspected the ABCs expansion in Aged (> 60 weeks) and Young (6 weeks) mice without autoimmune disease and collected the spleen and lymph nodes. The organ samples are used in comparing ABCs-inducing inflammatory phenotypes between two groups. Furthermore, measured the titer of autoantibodies from serum.

Results The extrafollicular (CD23-CD21-) ABCs (CD11c+ T-bet+) are dramatically increased in aged mice, and some inflammatory reactions are observed.

Conclusions We confirmed the inflammatory phenotype by ABCs in aged mice without autoimmune diseases. These results represent that ABCs could affect the autoimmune disease phenotype. Recently we revealed the transcription factor ‘Mef2d’ could regulate the cytokine IL-21. To figure out the mechanism of ABCs expansion in aged and autoimmunity, we will investigate whether the differentiation of ABCs can also be controlled by regulating IL-21 through Mef2d expression.