There is increasing interest in how immune cells, including those within the meninges at the blood–brain interface, influence brain function and mood disorders, but little data on humoral immunity in this context. Here, we show that in mice exposed to psychosocial stress, there is increased splenic B cell activation and secretion of the immunoregulatory cytokine interleukin (IL)-10. Meningeal B cells were prevalent in homeostasis but substantially decreased following stress, whereas Ly6Chi monocytes increased, and meningeal myeloid cells showed augmented expression of activation markers. Single-cell RNA sequencing of meningeal B cells demonstrated the induction of innate immune transcriptional programmes following stress, including genes encoding antimicrobial peptides that are known to alter myeloid cell activation. Cd19-/- mice, that have reduced B cells, showed baseline meningeal myeloid cell activation and decreased exploratory behaviour. Together, these data suggest that B cells may influence behaviour by regulating meningeal myeloid cell activation.
Graphical abstract
In stress (middle panel), in the periphery, we observed increased numbers of classical monocytes, neutrophils, plasma cells and regulatory B cells; plasma cell activation; naïve and memory B cell activation, and increased plasma G-CSF. In stressed meninges, we observed increased numbers of monocytes and neutrophils; increased activation of meningeal myeloid cells; decreased numbers of B cells, which were activated and had increased expression of antimicrobial peptides; and increased interferon-⍺ and interferon-γ signaling. These changes were associated with decreased exploratory behavior in a novel arena and anxious behavior on light–dark box testing. In CD19 deficiency (right hand panel), in the periphery, we observed increased neutrophils; decreased naïve and memory B cells; decreased regulatory B cells; decreased plasma cells; and increased plasma G-CSF. In meninges from Cd19-/- mice, we observed increased meningeal B cell activation; increased meningeal myeloid cell activation; increased meningeal neutrophils; and increased interferon-⍺ and interferon-γ signaling. These changes were associated with decreased exploratory behavior.
