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

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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.

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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.

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).

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany

    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 & Judith Alferink

  2. Cluster of Excellence EXC 1003, Cells in Motion, University of Münster, Münster, Germany

    Diana Ahmetspahic, Kathrin Schwarte, Mehrdad Rahbar Kooybaran & Judith Alferink

  3. Department of Behavioural Biology, University of Osnabrück, Osnabrück, Germany

    Oliver Ambrée

  4. Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, Düsseldorf, Germany

    Stefanie Scheu

  5. Alexianer Hospital for Psychiatry and Psychotherapy, Münster, Germany

    Judith Alferink

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  1. Diana Ahmetspahic
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  2. Kathrin Schwarte
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  3. Oliver Ambrée
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  4. Christian Bürger
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  5. Vladislava Falcone
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  6. Katharina Seiler
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  7. Mehrdad Rahbar Kooybaran
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  8. Laura Grosse
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  9. Fernand Roos
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  10. Julia Scheffer
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  11. Silke Jörgens
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  16. Judith Alferink
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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.

Corresponding author

Correspondence to Judith Alferink.

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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.

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Judith Alferink and Stefanie Scheu share last authorship.

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Ahmetspahic, D., Schwarte, K., Ambrée, O. et al. Altered B Cell Homeostasis in Patients with Major Depressive Disorder and Normalization of CD5 Surface Expression on Regulatory B Cells in Treatment Responders. J Neuroimmune Pharmacol 13, 90–99 (2018). https://doi.org/10.1007/s11481-017-9763-4

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