Altered B Cell Homeostasis in Patients with Major Depressive Disorder and Normalization of CD5 Surface Expression on Regulatory B Cells in Treatment Responders

Pro-inflammatory activity and cell-mediated immune responses have been widely observed in patients with major depressive disorder (MDD). Besides their well-known function as antibody-producers, B cells play a key role in inflammatory responses by secreting pro- and anti-inflammatory factors. However, homeostasis of specific B cell subsets has not been comprehensively investigated in MDD. In this study, we characterized circulating B cells of distinct developmental steps including transitional, naïve-mature, antigen-experienced switched, and non-switched memory cells, plasmablasts and regulatory B cells by multi-parameter flow cytometry. In a 6-weeks follow-up, circulating B cells were monitored in a small group of therapy responders and non-responders. Frequencies of naïve lgD⁺CD27^- B cells, but not lgD⁺CD27⁺ memory B cells, were reduced in severely depressed patients as compared to healthy donors (HD) or mildly to moderately depressed patients. Specifically, B cells with immune-regulatory capacities such as CD1d⁺CD5⁺ B cells and CD24⁺CD38^hi transitional B cells were reduced in MDD. Also Bm1-Bm5 classification in MDD revealed reduced Bm2' cells comprising germinal center founder cells as well as transitional B cells. We further found that reduced CD5 surface expression on transitional B cells was associated with severe depression and normalized exclusively in clinical responders. This study demonstrates a compromised peripheral B cell compartment in MDD with a reduction in B cells exhibiting a regulatory phenotype. Recovery of CD5 surface expression on transitional B cells in clinical response, a molecule involved in activation and down-regulation of B cell responses, further points towards a B cell-dependent process in the pathogenesis of MDD.