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+cd38hi 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.