Mechanical stimulation of human hair follicle outer root sheath cultures activates adjacent sensory neurons.

Mechanical stimuli, such as stroking or pressing on the skin, activate mechanoreceptors transmitting information to the sensory nervous system and brain. It is well accepted that deflection of the hair fiber that occurs with a light breeze or touch directly activates the sensory neurons surrounding the hair follicle, facilitating transmission of mechanical information. Here, we hypothesized that hair follicle outer root sheath cells act as transducers of mechanical stimuli to sensory neurons surrounding the hair follicle. Using electrochemical analysis on human hair follicle preparations in vitro, we were able to show that outer root sheath cells release ATP and the neurotransmitters serotonin and histamine in response to mechanical stimulation. Using calcium imaging combined with pharmacology in a coculture of outer root sheath cells with sensory neurons, we found that the release of these three molecules from hair follicle cells leads to activation of sensory neurons.

System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation.

Germinal center (GC) reactions are vital to the correct functioning of the adaptive immune system, through formation of high affinity, class switched antibodies. GCs are transient anatomical structures in secondary lymphoid organs where specific B cells, after recognition of antigen and with T cell help, undergo class switching. Subsequently, B cells cycle between zones of proliferation and somatic hypermutation and zones where renewed antigen acquisition and T cell help allows for selection of high affinity B cells (affinity maturation). Eventually GC B cells first differentiate into long-lived memory B cells (MBC) and finally into plasma cells (PC) that partially migrate to the bone marrow to encapsulate into long-lived survival niches. The regulation of GC reactions is a highly dynamically coordinated process that occurs between various cells and molecules that change in their signals. Here, we present a system-level perspective of T cell-mediated GC B cell differentiation, presenting and discussing the experimental and computational efforts on the regulation of the GCs. We aim to integrate Systems Biology with B cell biology, to advance elucidation of the regulation of high-affinity, class switched antibody formation, thus to shed light on the delicate functioning of the adaptive immune system. Specifically, we: i) review experimental findings of internal and external factors driving various GC dynamics, such as GC initiation, maturation and GCBC fate determination; ii) draw comparisons between experimental observations and mathematical modeling investigations; and iii) discuss and reflect on current strategies of modeling efforts, to elucidate B cell behavior during the GC tract. Finally, perspectives are specifically given on to the areas where a Systems Biology approach may be useful to predict novel GCBC-T cell interaction dynamics.