Thymic B Cells as a New Player in the Type 1 Diabetes Response

Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing beta cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs central tolerance- a key process in the deletion of autoreactive T and B cells during their development. For T cells, these studies have largely focused on medullary thymic epithelial cells (mTECs) critical for the effective negative selection of autoreactive T cells in the thymus. Recently, a new cellular player that impacts positively or negatively on the deletion of autoreactive T cells during their development has come to light, thymic B cells. Normally a small population within the thymus of mouse and man, thymic B cells expand in T1d as well as other autoimmune conditions, reside in thymic ectopic germinal centres and secrete autoantibodies that bind selective mTECs precipitating mTEC death. In this review we will discuss the ontogeny, characteristics and functionality of thymic B cells in healthy and autoimmune settings. Furthermore, we explore how in silico approaches may help decipher the complex cellular interplay of thymic B cells with other cells within the thymic microenvironment leading to new avenues for therapeutic intervention.

Automated summary

Type 1 diabetes is a result of sustained autoreactive T and B cell response towards insulin-producing beta cells in the islets of Langerhans. Among the many investigations addressing genetic or cellular changes related to central tolerance, thymic B cells have emerged as a new cellular player with a significant impact on the deletion of autoreactive T cells during their development. These thymic B cells can expand in T1D and other autoimmune conditions, leading to the secretion of autoantibodies that bind selective mTECs and induce their death.