Relationship Between B Cells And Cistanche in Neuroinflammation
Mar 22, 2023
Abstract:In recent years, the role of B cells in neurological diseases has greatly expanded our understanding of the mechanisms of neuroinflammation. The success of B-cell depletion therapy in patients with central nervous system diseases such as optic neuromyelitis and multiple sclerosis highlights the importance of neuroimmune crosstalk in the inflammatory process. While B cells are essential for the adaptive immune system and antibody production, they are also major contributors to the pro-inflammatory and anti-inflammatory cytokine responses in many inflammatory diseases. B cells can cause neurological diseases through peripheral immune mechanisms, including the production of cytokines and antibodies, or through central nervous system mechanisms following compartmentalization. Emerging evidence suggests that abnormal populations of pro-inflammatory or anti-inflammatory B cells contribute to neural processes, including glial activation, which has been implicated in the pathogenesis of several neurodegenerative diseases. In this review, we summarize the recent findings on the involvement of B cells in neuroinflammatory diseases and discuss the evidence supporting a pathogenic immunomodulatory function of B cells in neurological diseases, highlighting the importance of B-cell targeted therapy. The discovery of the use of cistanche extract to treat neuropathic diseases is also being explored.
Keywords:B cell; neuro inflflammation; neurological disorders; cytokines; multiple sclerosis; Parkinson’s disease; Alzheimer’s disease; cistanche
1. Introduction
The central nervous system (CNS) has traditionally been considered a strictly immunologically privileged site due to the absence of lymphatic vessels and specialized antigen-presenting cells in the brain parenchyma, as well as physical barriers that prevent circulating immune cells from entering the CNS. As the understanding of the interaction between the peripheral immune system and the central nervous system continues to expand, subsequent research has redefined the concept of immune privilege within the central nervous system. Although the CNS continues to be considered an immunological privilege, it is now clear that under healthy homeostasis conditions, low numbers of lymphocytes enter the CNS lymphatic vessels and support CNS immune surveillance. One channel through which cells travel through the central nervous system is through cerebrospinal fluid (CSF). The choroid plexus, the main source of cerebrospinal fluid, is made up of epithelial cells that form a tight barrier separating blood from the central nervous system. Drainage of CSF-interstitial fluid (ISF) follows specific pathways in the central nervous system, including the ventricles, subarachnoid space, parenchyma, and subcortical regions, and flows into the lymph nodes deep in the neck. This functional link between the central nervous system and the cervical lymph nodes further supports the concept of neuroimmune crosstalk. In the damaged or inflamed central nervous system, lymphocytes (including T and B cells) are multiplied several times throughout parenchyma, CSF-ISF, perivascular, and meningeal Spaces due to antigen flow to the lymph nodes or disruption of the blood-brain barrier. The new role of the adaptive immune system in the pathophysiology of neurological diseases has led to the successful development of therapies specifically targeting the adaptive immune system, including B-cell depletion of monoclonal antibodies. And drug treatments, such as cistanche, to boost B-cell activity, which in turn increases nerve cell immunity.
Pic: Cistaches Extract
In this review, we summarize the immune properties of B cells and the central nervous system and discuss the evidence supporting the emerging concept that B cells play a key role in regulating adaptive and innate immune responses in various neurological disorders. B cells are known to play a role in certainneuroinflammatory Settings, including optic neuromyelitis and autoimmune encephalitis, where B cells produce antibodies against CNS antigens that cause damage [12-14]. Emerging evidence suggests that a range of neurodegenerative diseases also lead to immune cell activation, and in this review, we focus on B-cell-driven neuroinflammatory responses in disease that have recently provided insights into how the immune system contributes to the pathogenesis of neurological diseases, These include multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD). Cistanche contains creinoside, which can significantly reduce MDA content in brain tissue, heart and liver of subacute aging model mice induced by D-galactose, significantly increase telomerase activity in heart and brain tissue, enhance phagocytosis function of peritoneal macrophages, and significantly increase lymphocyte proliferation response and IL-2 content in peripheral blood. It showed that litenoside can enhance immune function.
2. B cell biology
Together, B cells and T cells form the adaptive immune system, whose primary role is to protect the body from harmful pathogens. Foreign substances that enter the body are recognized as antigens and cause an immune response in which B cells and T cells combine with other cell types of the immune system to selectively recognize and eliminate antigens.
B cells develop in the fetal liver and postnatal bone marrow, where they undergo several well-defined stages of maturation and differentiation in response to induction signals. B cells mature from hematopoietic stem cells, give rise to progenitor B cells, precursor B cells, immature naive, transition, and then mature naive B cells. In the presence of specific antigens and with the help of T follicular helper cells, mature naive B cells now residing in secondary lymphoid organs are activated and differentiate into antibody-producing plasma and memory B cells
Pic: Effects of cistanche improve immunity
3. Immune regulation
The brain and spinal cord are isolated from the peripheral immune response by two main barriers, the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier, which regulate the passage of immune mediators and immune cells into the central nervous system. Under homeostasis, white blood cells such as memory T cells penetrate the central nervous system and flow through the cerebrospinal fluid in the meninges. CSF and lymphatic vessels allow the lowest level of traffificking peripheral immunesystem of white blood cells leading to central nervous system surveillance. However, under pathological conditions such as cerebrovascular and neurodegenerative diseases, white blood cell count traffificking into the brain parenchyma increases, and activation of innate immune cells such as mast cells further compromises the integrity of the blood-brain barrier. These events create an unbalanced pro-inflammatory and anti-inflammatory environment.
The innate immune response of the central nervous system is often characterized by the reactivity of glial cells, particularly microglia and astrocytes. Glial cells are able to breach the blood-brain barrier as other innate immune cells, such as mast cells, are activated. Similarly, astrocytes exhibit functional heterogeneity in both homeostasis and disease states, which may be neurotoxic or neuroprotective. Together, microglia and astrocytes can adopt pro-inflammatory or anti-inflammatory phenotypes to prevent or exacerbate disease. Studies have shown that reactive microglia and astrocytes promote disease by up-regulating the transcriptional activity of pro-inflammatory genes. Desert Cistanche polysaccharide can reduce MDA content in brain, heart and liver of immunocompromised animal models, increase telomerase activity in heart and brain tissue, phagocytosis function of peritoneal macrophages, proliferation response of lymphocytes, IL-2 content in spleen T lymphocytes and calcium ion concentration in thymus cells. These indicators indicate that cistanche polysaccharide can enhance immune function.
Pic: Cistanches Benefits
4. B cells in neurological diseases
MS is a chronic inflammatory demyelinating disease characterized by demyelinating lesions of the brain and spinal cord. Although MS is primarily considered a white matter disease, both MRI and neuropathology studies of the brain have revealed extensive grey matter involvement, particularly in cortical areas, even in the early stages of the disease, and the extent of grey matter involvement correlates with physical and cognitive symptoms, and becomes more severe in progressive forms of the disease. In addition to demyelination, activation of microglia and astrocytes and axon loss are commonly associated with disease activity. Although the onset and clinical course of the disease may vary, approximately 90% of patients present with relapsing-remitting MS (RRMS), in which patients have periods of relapse (new or worsening neurological symptoms) and periods of remission. For most RRMS patients, symptoms eventually worsen without remission after a certain number of years, which is defined as secondary progressive MS. Individuals with cumulative disability from the previous group without recurrence have a variant of the disease known as primary progressive MS.
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5. Further consideration and conclusion
Although generally speaking, B-cell function in neurological diseases has not been extensively studied to date, the success of anti-CD20 depleting antibodies against MS is encouraging aging and indicates a clear need for further research into immunomodregulatory function both inside and outside the central nervous system in the context of neurodegenerative diseases. Total cistanche glycosides can significantly enhance the antibody production, the number of T lymphocytes in peripheral blood, phagocytic function of peritoneal macrophages, and delayed hypersensitivity in mice damaged by 60 Co y rays, and can also improve the thymus index, spleen index and survival rate of exposed mice, indicating that total cistanche glycosides have a strong protective effect on the immune function of radiation-damaged mice. A potential model for the B-cell drive mechanism is that peripheral B cells secrete immunomodulatory molecules such as cytokines or antibodies that invade the central nervous system through the dysfunctional blood-brain barrier. On the other hand, as MS has shown, B cells themselves may infiltrate the central nervous system and directly cause glial reactions or neuronal damage by secreting inflammatory proteins. These insights compel us to further decipher neural immune crossinuations, which will certainly provide further guidance for not only improving the effectiveness of current B-cell targeting therapies, but also for the discovery of the next generation of therapies.
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