New findings: The interaction of the brain and spleen helps with the production of antibodies.

The spleen is the largest peripheral lymphoid organ of the human body. Its essence is composed of red pulp and white pulp. It has the functions of hematopoiesis and blood filtration. It is also an important place for lymphocyte migration and immune response after antigen stimulation.a new study in the April 29th issue of nature suggests that complex ways in which the brain and body interact can affect many aspects of health, from mood to immune function.the spleen is a target of top-down brain control.for centuries, the interaction between the brain and the body has aroused the interest of scientists and philosophers.in ancient Greece, Galen described the spleen as the source of black bile, believing that excessive secretion of black bile led to depression.on April 29, researchers found that the complex way in which the brain interacts with the body can affect many aspects of health, from mood to immune function.as a part of the lymphatic system, spleen contributes to immune defense; organs are the main centers in the acquired immune branch of the immune system to initiate the required activities, which can deal with a defense against specific pathogenic factors.the spleen is a target of top-down control of the brain. Zhang et al. Wrote in nature that they revealed a level of top-down control regulating the acquired immune system, and raised people's understanding of the relationship between brain and spleen to a new level.the contribution of the spleen to the immune response mainly occurs in its white pulp area, where immune cells from all over the body supply peptide fragments called antigens like immune cells called T cells.If a T cell binds and recognizes this antigen, it may indicate that an abnormal cell or an alien invader has appeared, which activates T cells, which in turn activate T cells, which in turn activate B-cell immune cells, which differentiate into plasma cells and secrete antibodies against the antigen presented, which are released into the blood to resist infection.the brain controls antibody production, and spleen activity is controlled by the autonomic nervous system (part of the nervous system that regulates organs). More specifically, the spleen is mainly controlled by the sympathetic branches of the autonomic nervous system, which is related to the "attack and escape" reaction.however, little has been known about the possible connection of the autonomic nerves of the spleen to control the upstream brain regions of the spleen and the resulting acquired immunity.an early study in mice showed that stimulation of the ventral tegmental area (part of the brain's reward circuit) enhances the immune response and helps to ward off harmful bacteria.Zhang and his colleagues developed a surgical technique to remove nerves from the spleen of mice, mainly to remove input from the autonomic nervous system and avoid top-down brain to spleen control.after the operation, animals were injected with antigen, and plasma cells produced a large number of antibodies against the antigen, while the control group underwent a "sham" operation without nerve removal.this increase did not occur in denervated mice, suggesting that splenic nerve activity can regulate the formation of plasma cells and thus regulate acquired immunity. In this experiment,researchers investigated the molecular mechanisms that might be required for plasma cell formation. They studied various expressions of the receptors of acetylcholine linking neurotransmitters. Acetylcholine, a neurotransmitter, is a key signal component of the autonomic nervous system. Zhang et al. Pointed out that B cells express a type of acetylcholine receptor called saline alkali receptor. the researchers found that the protein subunit of this receptor contains a subunit called chrna9. in order to test the role of the saline alkali receptor containing chrna9 in plasma cell formation, Zhang et al. Transplanted hematopoietic stem cells capable of producing immune cells into mice that had already removed their own hematopoietic stem cells. When stem cells removed from mice were involved in the lack of gene encoding chrna9, compared with those animals receiving antigen injection and gene intact stem cell transplantation, these stem cells were able to generate immune cells Animals produce less plasma cells after injection of antigen, which indicates that the formation of plasma cells requires the presence of saline alkali receptors. when a T cell called CD4 + T cell is activated by antigen recognition, it secretes acetylcholine in response to the hormone norepinephrine. these T cells act as a "relay" between the release of norepinephrine from the splenic nerve and the subsequent acetylcholine dependence of plasma cells. to find out the neural circuits connecting the spleen and the brain, the researchers used a retrograde tracking method, relying on monitoring the expression of a virus encoded fluorescent protein, which can 'jump' through synapses connecting neurons. this allows Zhang and his colleagues to track all upstream inputs from a given nerve cell in a spleen. the researchers identified two key brain regions (the amygdala and the paraventricular nucleus of the inferior colliculus), containing neurons that connect the splenic nerve. these regions are the main centers that contain responses to psychological stress (such as fear or threat situations), and play a crucial role in regulating the production of neuroendocrine hormones, such as a pathway called the hypothalamus pituitary adrenal axis. a group of nerve cells in these two regions release adrenocorticotropic hormone, which plays a key role in initiating the body's response to stress. In order to find out whether the adrenocorticotropic hormone producing neurons affect the spleen, Zhang et al. Activated these neurons with photogenetic technology and evaluated their discharge by monitoring and using electrophysiological records Whether this will affect the activation of splenic nerve. this provides a crucial evidence for the connection between the brain and the spleen, because this stimulation increases the discharge of the splenic nerve cells. the researchers pointed out that inhibition or ablation of corticotropin producing neurons in two brain regions could damage the formation of plasma cells after antigen injection. on the contrary, the activation of neurons stimulated the formation of this plasma cell. although these circuit based experimental methods provide key evidence for the existence of the brain spleen axis, researchers also need to test their models using appropriate interventions that activate the "stress center" of the brain. however, neurons in the central and paraventricular nuclei of the amygdala play a role in a pathway that results in the secretion of glucocorticoids in the adrenal stress response, which has potential immunosuppressive effects. therefore, the researchers believe that the concentration of glucocorticoid secreted by the adrenal gland may depend on the severity of stress. in order to avoid possible glucocorticoid driven immunosuppression that may interfere with the analysis of antibody production, Zhang et al. Studied mice placed on a high transparent platform; this provided a behavior state that caused only moderate stress. after antigen injection, this condition, but not another setting that causes more severe stress, leads to the production of antigen-specific antibodies. thus, it is demonstrated that the production of this antibody depends on the corticotropin producing neurons in the brain circuit they described. there is growing evidence that immune system disorders play a bottom-up role in promoting certain behaviors associated with neuropsychiatric disorders. the research by Zhang and his colleagues provides insights in another direction - how the brain controls the function of the immune system from top to bottom. future research will need to investigate whether this particular brain spleen circuit exists in humans. the results reveal an exciting possibility that activation of certain brain regions (through behavioral intervention or selective stimulation using neural regulatory techniques such as transcranial magnetic stimulation) can regulate the immune system. back to Galen's point of view, he was right that the spleen is a key part of the brain and body, but his idea of how the spleen causes depression now gives way to the new idea of how the brain regulates the antibodies to recovery. reference: [1] [2] recommended reading: fighting against the epidemic situation, translational medicine network content team series reports: [Nature] new discovery: the destruction of blood-brain barrier is also an early marker of Alzheimer's disease [Focus] why covid-19 patients feel very comfortable under hypoxia? 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