Sleep restriction prior to antigen exposure does not alter the T cell receptor repertoire but impairs germinal center formation during a T cell-dependent B cell response in murine spleen

Cornelia Tune; Julia Hahn; Stella E Autenrieth; Martin Meinhardt; Rene Pagel; Andrea Schampel; Lisa-Kristin Schierloh; Kathrin Kalies; Juergen Westermann

doi:10.1016/j.bbih.2021.100312

Sleep restriction prior to antigen exposure does not alter the T cell receptor repertoire but impairs germinal center formation during a T cell-dependent B cell response in murine spleen

Brain Behav Immun Health. 2021 Jul 30:16:100312. doi: 10.1016/j.bbih.2021.100312. eCollection 2021 Oct.

Authors

Cornelia Tune¹, Julia Hahn², Stella E Autenrieth², Martin Meinhardt¹, Rene Pagel¹, Andrea Schampel¹, Lisa-Kristin Schierloh¹, Kathrin Kalies¹, Juergen Westermann¹

Affiliations

¹ Institute of Anatomy, University of Luebeck, Germany.
² Department of Internal Medicine II, University of Tuebingen, Germany.

Abstract

It is well known that sleep promotes immune functions. In line with this, a variety of studies in animal models and humans have shown that sleep restriction following an antigen challenge dampens the immune response on several levels which leads to e.g. worsening of disease outcome and reduction of vaccination efficiency, respectively. However, the inverse scenario with sleep restriction preceding an antigen challenge is only investigated in a few animal models where it has been shown to reduce antigen uptake and presentation as well as pathogen clearance and survival rates. Here, we use injection of sheep red blood cells to investigate the yet unknown effect on a T cell-dependent B cell response in a well-established mouse model. We found that 6 h of sleep restriction prior to the antigen challenge does not impact the T cell reaction including the T cell receptor repertoire but dampens the development of germinal centers which correlates with reduced antigen-specific antibody titer indicating an impaired B cell response. These changes concerned a functionally more relevant level than those found in the same experimental model with the inverse scenario when sleep restriction followed the antigen challenge. Taken together, our findings showed that the outcome of the T cell-dependent B cell response is indeed impacted by sleep restriction prior to the antigen challenge which highlights the clinical significance of this scenario and the need for further investigations in humans, for example concerning the effect of sleep restriction preceding a vaccination.

Keywords: Antigen presentation; BCZ, B cell zone; CCL, C–C motif ligand; CCR, C–C motif receptor; CD, cluster of differentiation; CIITA, class II major histocompatibility complex transactivator; CXCL, C-X-C motif ligand; FDR, false discovery rate; GC, germinal center; Germinal center; IFN, interferon; IL, interleukin; IgG, Immunglobulin G; MHC-II, major histocompatibility complex II; Mouse; RP, red pulp; SD, standard deviation; SLO, secondary lymphoid organ; SRBC, sheep red blood cells; Sheep red blood cells; Sleep deprivation; Spleen; T cell-dependent B cell response; TCR, T cell receptor; TCR-R, T cell receptor repertoire; TCZ, T cell zone; Tfh, follicular T helper cells.