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

Abstract

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 lgDCD27 B cells, but not lgDCD27 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 CD1dCD5 B cells and CD24CD38 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.

Ligands and receptors of the TNF superfamily are decreased in major depression and during early antidepressant therapy

“…One may speculate that the increase in B cells observed in depressed patients (Maes et al, 1992), accompanied with the up-regulation of BAFF receptors, leads to auto-regulatory reductions in concentrations of BAFF in major depression. On the opposite, the reduction of naïve B cells in major depression (Ahmetspahic et al, 2017) may be a consequence following the reductions in BAFF-concentrations and the missing anti-apoptotic features of BAFF.…”

Involvement of Innate and Adaptive Immune Systems Alterations in the Pathophysiology and Treatment of Depression

“…In addition to increased peripheral monocytes, atrophy of astrocytes, and increased activation of microglia, MDD patients also exhibit decreased numbers of circulating T cells and a reduction in regulatory B cells ( Ahmetspahic et al, 2018 ), suggestive of a dysregulation of the adaptive immune system in MDD patients. In addition, T cells from MDD patients have a reduced capacity to respond to stimulation, indicative of an immunosuppressed phenotype of T cells in MDD ( Herbert and Cohen, 1993 ; Zorrilla et al, 2001 ; Irwin and Miller, 2007 ).…”

Severe, But Not Moderate Asthmatics Share Blood Transcriptomic Changes With Post-Traumatic Stress Disorder And Depression.

“…The latter is perhaps more likely as neutrophils have been demonstrated to be activated in patients with MDD and asthma 73,74 . Furthermore, B cell homeostasis is altered in individuals with MDD and B cells play a crucial role in regulating the hyperactivity of airways in asthma 75,76,77,78 . Likewise, there is generally increased activity and larger numbers of monocytes in MDD and asthma compared to healthy subjects 79,80,81,82 .…”