The bidirectional relationship of depression and disturbances in B cell homeostasis: Double trouble

Major depressive disorder (MDD) is a recurrent, persistent, and debilitating neuropsychiatric syndrome with an increasing morbidity and mortality, representing the leading cause of disability worldwide. The dysregulation of immune systems (including innate and adaptive immune systems) has been identified as one of the key contributing factors in the progression of MDD. As the main force of the humoral immunity, B cells have an essential role in the defense against infections, antitumor immunity and autoimmune diseases. Several recent studies have suggested an intriguing connection between disturbances in B cell homeostasis and the pathogenesis of MDD, however, the B-cell-dependent mechanism of MDD remains largely unexplored compared to other immune cells. In this review, we provide an overview of how B cell abnormality regulates the progression of MMD and the potential consequence of the disruption of B cell homeostasis in patients with MDD. Abnormalities of B-cell homeostasis not only promote susceptibility to MDD, but also lead to an increased risk of developing infection, malignancy and autoimmune diseases in patients with MDD. A better understanding of the contribution of B cells underlying MDD would provide opportunities for identification of more targeted treatment approaches and might provide an overall therapeutic benefit to improve the long-term outcomes of patients with MDD.