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Journal of Neuroimmune Pharmacology

, Volume 13, Issue 1, pp 90–99 | Cite as

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

  • Diana Ahmetspahic
  • Kathrin Schwarte
  • Oliver Ambrée
  • Christian Bürger
  • Vladislava Falcone
  • Katharina Seiler
  • Mehrdad Rahbar Kooybaran
  • Laura Grosse
  • Fernand Roos
  • Julia Scheffer
  • Silke Jörgens
  • Katja Koelkebeck
  • Udo Dannlowski
  • Volker Arolt
  • Stefanie Scheu
  • Judith AlferinkEmail author
ORIGINAL ARTICLE

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 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.

Keywords

Major depressive disorder Depression Transitional B cells Regulatory B cells Immunoregulation Immune response Immune cells Immune system 

Notes

Acknowledgements

We sincerely thank all participants who donated blood in order to realize this study. In addition, we greatly appreciate Hildegard Stücker for assisting in patient and healthy donor recruitment and blood sampling.

Author Contributions

JA, and SS conceptualized the study, designed research, analyzed and interpreted the data, and wrote the manuscript. DA performed research, collected, analyzed and interpreted the data, and wrote the manuscript. KS and MRK performed research and collected data. OA and CB advised for statistical analysis and critically edited the manuscript. SJ, KK, and LG organized patient recruitment and provided clinical information LG. CB, VF, KS, FR and JS were responsible for patient care and provided clinical information. UD, KK, VA, and SJ helped to conceptualize the project, and critically edited the manuscript.

Funding

The work of JA has been funded by the DFG EXC 1003, Grant FF-2014-01 Cells in Motion–Cluster of Excellence, Münster, Germany. UD is funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5–1; grant SFB-TRR58, Project C09) and the Interdisciplinary Center for Clinical Studies (IZKF, grant Dan3/012/17).

Compliance with Ethical Standards

Conflict of Interest

The authors declared no conflict of interest.

Disclosures

JA, DA, KS, OA, CB, VF, KS, MRK, LG, FR, JS, UD, KK, SJ, and SS have no financial disclosures. VA is member of advisory boards and/or gave presentations for the following companies: Astra-Zeneca, Eli Lilly, Janssen-Organon, Lundbeck, Otsuka, Servier, and Trommsdorff.

Supplementary material

11481_2017_9763_MOESM1_ESM.pdf (684 kb)
ESM 1 (PDF 683 kb)
11481_2017_9763_MOESM2_ESM.pdf (634 kb)
ESM 2 (PDF 634 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Diana Ahmetspahic
    • 1
    • 2
  • Kathrin Schwarte
    • 1
    • 2
  • Oliver Ambrée
    • 1
    • 3
  • Christian Bürger
    • 1
  • Vladislava Falcone
    • 1
  • Katharina Seiler
    • 1
  • Mehrdad Rahbar Kooybaran
    • 1
    • 2
  • Laura Grosse
    • 1
  • Fernand Roos
    • 1
  • Julia Scheffer
    • 1
  • Silke Jörgens
    • 1
  • Katja Koelkebeck
    • 1
  • Udo Dannlowski
    • 1
  • Volker Arolt
    • 1
  • Stefanie Scheu
    • 4
  • Judith Alferink
    • 1
    • 2
    • 5
    Email author
  1. 1.Department of Psychiatry and PsychotherapyUniversity of MünsterMünsterGermany
  2. 2.Cluster of Excellence EXC 1003, Cells in MotionUniversity of MünsterMünsterGermany
  3. 3.Department of Behavioural BiologyUniversity of OsnabrückOsnabrückGermany
  4. 4.Institute of Medical Microbiology and Hospital HygieneUniversity of DüsseldorfDüsseldorfGermany
  5. 5.Alexianer Hospital for Psychiatry and PsychotherapyMünsterGermany

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