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Responsible Editor | Xi antibody is expressed as a membrane protein on the surface of B cells to specifically recognize antigens before being secreted outside the cell, so it is also called B cell receptor (BCR)
.
During the development of B cells, a series of random rearrangement events of VDJ genes occurred in the BCR genome region, which then formed a highly complex and diverse BCR immune repertoire
.
The diversity of BCR repertoire ensures that the B cells in our body can recognize a variety of non-self substances, including various pathogenic microorganisms, and make corresponding protective immune responses
.
However, random rearrangement of VDJ genes can also produce BCRs that can recognize their own substances
.
Under normal circumstances, B cell precursors (pre-B) and immature B cells that express self-reactive BCRs will be recognized by a set of self-antigens called central tolerance (central tolerance).
The tolerance mechanism is eliminated to achieve negative selection, which in turn limits the development and maturation of autoreactive B cells
.
The dysregulation of negative screening of autoreactive B cells can be accompanied by a variety of autoimmune diseases, such as multiple sclerosis (MS), systemic lupus erythematosus (SLE) and so on
.
Since the discovery of B cells in mammals, it is believed that the important immunological process of B cell development and central tolerance is only carried out in the bone marrow
.
Therefore, autoantigens need to be present in the bone marrow at a higher abundance to effectively trigger negative screening to eliminate autoreactive B cells
.
For example, the myelin oligodendrocyte glycoprotein (MOG), which is specifically expressed in the central nervous system (CNS), has a low abundance in the bone marrow and cannot activate the negative screening mechanism in the bone marrow
.
Consistent with this finding, the MOG antibody gene knock-in (IgHMOG knock-in, also known as Th) established by genetic methods has a large number of mature B cells (Litzenburger et al.
, JEM 1998)
.
However, recent studies have found that immune cells such as B cells can appear in the meninges through lymphatic vessels (Louveau et al.
, Nature 2015; Keren-Shaul et al.
, Cell 2017; Mundt et al.
, Sci.
Immunol.
2019), It shows that MOG-responsive B cells also have the opportunity to enter the CNS area and contact MOG protein
.
But it is strange that the Th mouse model did not develop experimental autoimmune encephalomyelitis (EAE), a typical autoimmune disease of the nervous system (Litzenburger et al.
, 1998)
.
This phenomenon suggests that there may be other important B cell immune tolerance regulatory mechanisms in our body
.
On October 8, 2021, the Xu Heping research group of West Lake University and He Danyang's research group jointly published a research paper entitled Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges in Immunity magazine
.
The research results revealed a new way for B lymphocytes to carry out development and negative screening in the meninges (Figure 1), rewriting the current theory that mammalian B lymphocytes only carry out development and central tolerance screening in the bone marrow
.
Figure 1.
Schematic diagram of the summary of meningeal B lymphocyte development and negative screening studies In order to clarify whether autoreactive B cells interact with CNS antigens in the meninges, the research team first used a mouse model to analyze the molecular characteristics of B cells in the meninges
.
The results of the study surprisingly found that in addition to mature B cells, mouse meninges mainly contain B cells in the early stages of development, including progenitor B cells (pro-B), pre-B and immature B cells
.
The classic theory in textbooks believes that these early developing B cells only stably exist in the bone marrow in adult mammals
.
In order to clarify that meningeal B cells are not unique to the mouse model, the project team further analyzed the meningeal B cells of Chinese macaques
.
The results of the study confirmed that there are also B cells at different developmental stages in the meninges of the macaque, a higher primate animal, indicating that the developmental pathways of meningeal B cells are conservative
.
Later, the research team used conjoined animal models, regional bone marrow transplantation models, and genetic cell fate tracing methods to find that meningeal development B cells are mainly differentiated from hematopoietic stem cells in the skull
.
The project team further researched and found that compared with wild-type animal models, there are no MOG-reactive B cells in the meninges of Th mice; however, knocking out the Mog gene through genetic means can restore MOG-reactive B cells in the meninges of Th mice.
It is proved that the developing B cells in the meninges will undergo negative screening mediated by CNS-specific autoantigens
.
In summary, this study reveals that there is a conservative early B cell development pathway in the meninges; developmental B cells that recognize CNS autoantigens in the meninges will undergo negative screening and then be eliminated to ensure the formation of a non-self-reactive CNS immune microenvironment
.
This research work has revised the theoretical knowledge about the development and selection of B lymphocytes in current textbooks, and is of great significance for the establishment and improvement of the basic theories related to the development and selection of B lymphocytes
.
Elucidating the regulation mechanism of meningeal B cell development and tolerance will bring a new perspective for humans to explore and understand the pathogenesis of multiple sclerosis and other autoimmune diseases, intracranial infectious diseases, and central nervous system B lymphoma
.
It is reported that this research work was first published in the preprint bioRxiv magazine (https:// on June 3, 2021
.
Researchers Xu Heping and He Danyang of West Lake University are the co-corresponding authors of the paper.
Doctoral students Wang Yan and Chen Tianyu of West Lake University and research assistant Xu De are the co-first authors of this paper
.
Original link: https://doi.
org/10.
1016/j.
immuni.
2021.
09.
016 Attached to the introduction of the research group and recruitment information The Laboratory of Systemic Immunology of West Lake University is dedicated to exploring the key molecular mechanisms and key molecular mechanisms that regulate the humoral immune response and mucosal inflammation Network
.
Based on the organic integration and utilization of genetic animal models, clinical samples and cutting-edge bioinformatics, it focuses on the interaction mechanism of the immune and nervous system and other tissue-specific microenvironments in the inflammatory response.
.
With the support of the National Overseas High-level Talents Program, the National Natural Science Foundation of China Joint Fund Key Project, and the Ministry of Science and Technology Key R&D Program, various projects in the laboratory are progressing smoothly.
There is an urgent need for young talents (postdoctoral, doctoral students, scientific research assistants).
Join us to grow and develop together! The research interest of He Danyang's research group at West Lake University is to explore the interaction mechanism between the immune and nervous systems
.
On the basis of organic integration of genetics, cell biology, and system biology, the immune regulation mechanism in neurodevelopment and disease will be systematically explored
.
It is hoped that the research results can contribute to a comprehensive understanding of neurodevelopmental regulatory networks and the discovery of new targets for the treatment of cognitive impairment and neurodegenerative diseases
.
The main research directions include: (1) exploring the functions and molecular mechanisms of microglia in neurodevelopment and nervous system diseases; (2) revealing the function of meningeal immunity in central nervous system homeostasis and inflammation; (3) systemic Map the molecular and cellular network of the intestinal glial immune circuit in intestinal homeostasis and inflammation
.
The laboratory currently has post-doctoral, doctoral and research assistant positions, welcome to contact us! Resume delivery (If you are interested, please send your resume and other materials to): https://jinshuju.
net/f/ZqXwZt or scan the QR code to deliver your resume.
Platemaker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article All, personal forwarding and sharing are welcome, reprinting is prohibited without permission, the author has all legal rights, and offenders must be investigated
.
.
During the development of B cells, a series of random rearrangement events of VDJ genes occurred in the BCR genome region, which then formed a highly complex and diverse BCR immune repertoire
.
The diversity of BCR repertoire ensures that the B cells in our body can recognize a variety of non-self substances, including various pathogenic microorganisms, and make corresponding protective immune responses
.
However, random rearrangement of VDJ genes can also produce BCRs that can recognize their own substances
.
Under normal circumstances, B cell precursors (pre-B) and immature B cells that express self-reactive BCRs will be recognized by a set of self-antigens called central tolerance (central tolerance).
The tolerance mechanism is eliminated to achieve negative selection, which in turn limits the development and maturation of autoreactive B cells
.
The dysregulation of negative screening of autoreactive B cells can be accompanied by a variety of autoimmune diseases, such as multiple sclerosis (MS), systemic lupus erythematosus (SLE) and so on
.
Since the discovery of B cells in mammals, it is believed that the important immunological process of B cell development and central tolerance is only carried out in the bone marrow
.
Therefore, autoantigens need to be present in the bone marrow at a higher abundance to effectively trigger negative screening to eliminate autoreactive B cells
.
For example, the myelin oligodendrocyte glycoprotein (MOG), which is specifically expressed in the central nervous system (CNS), has a low abundance in the bone marrow and cannot activate the negative screening mechanism in the bone marrow
.
Consistent with this finding, the MOG antibody gene knock-in (IgHMOG knock-in, also known as Th) established by genetic methods has a large number of mature B cells (Litzenburger et al.
, JEM 1998)
.
However, recent studies have found that immune cells such as B cells can appear in the meninges through lymphatic vessels (Louveau et al.
, Nature 2015; Keren-Shaul et al.
, Cell 2017; Mundt et al.
, Sci.
Immunol.
2019), It shows that MOG-responsive B cells also have the opportunity to enter the CNS area and contact MOG protein
.
But it is strange that the Th mouse model did not develop experimental autoimmune encephalomyelitis (EAE), a typical autoimmune disease of the nervous system (Litzenburger et al.
, 1998)
.
This phenomenon suggests that there may be other important B cell immune tolerance regulatory mechanisms in our body
.
On October 8, 2021, the Xu Heping research group of West Lake University and He Danyang's research group jointly published a research paper entitled Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges in Immunity magazine
.
The research results revealed a new way for B lymphocytes to carry out development and negative screening in the meninges (Figure 1), rewriting the current theory that mammalian B lymphocytes only carry out development and central tolerance screening in the bone marrow
.
Figure 1.
Schematic diagram of the summary of meningeal B lymphocyte development and negative screening studies In order to clarify whether autoreactive B cells interact with CNS antigens in the meninges, the research team first used a mouse model to analyze the molecular characteristics of B cells in the meninges
.
The results of the study surprisingly found that in addition to mature B cells, mouse meninges mainly contain B cells in the early stages of development, including progenitor B cells (pro-B), pre-B and immature B cells
.
The classic theory in textbooks believes that these early developing B cells only stably exist in the bone marrow in adult mammals
.
In order to clarify that meningeal B cells are not unique to the mouse model, the project team further analyzed the meningeal B cells of Chinese macaques
.
The results of the study confirmed that there are also B cells at different developmental stages in the meninges of the macaque, a higher primate animal, indicating that the developmental pathways of meningeal B cells are conservative
.
Later, the research team used conjoined animal models, regional bone marrow transplantation models, and genetic cell fate tracing methods to find that meningeal development B cells are mainly differentiated from hematopoietic stem cells in the skull
.
The project team further researched and found that compared with wild-type animal models, there are no MOG-reactive B cells in the meninges of Th mice; however, knocking out the Mog gene through genetic means can restore MOG-reactive B cells in the meninges of Th mice.
It is proved that the developing B cells in the meninges will undergo negative screening mediated by CNS-specific autoantigens
.
In summary, this study reveals that there is a conservative early B cell development pathway in the meninges; developmental B cells that recognize CNS autoantigens in the meninges will undergo negative screening and then be eliminated to ensure the formation of a non-self-reactive CNS immune microenvironment
.
This research work has revised the theoretical knowledge about the development and selection of B lymphocytes in current textbooks, and is of great significance for the establishment and improvement of the basic theories related to the development and selection of B lymphocytes
.
Elucidating the regulation mechanism of meningeal B cell development and tolerance will bring a new perspective for humans to explore and understand the pathogenesis of multiple sclerosis and other autoimmune diseases, intracranial infectious diseases, and central nervous system B lymphoma
.
It is reported that this research work was first published in the preprint bioRxiv magazine (https:// on June 3, 2021
.
Researchers Xu Heping and He Danyang of West Lake University are the co-corresponding authors of the paper.
Doctoral students Wang Yan and Chen Tianyu of West Lake University and research assistant Xu De are the co-first authors of this paper
.
Original link: https://doi.
org/10.
1016/j.
immuni.
2021.
09.
016 Attached to the introduction of the research group and recruitment information The Laboratory of Systemic Immunology of West Lake University is dedicated to exploring the key molecular mechanisms and key molecular mechanisms that regulate the humoral immune response and mucosal inflammation Network
.
Based on the organic integration and utilization of genetic animal models, clinical samples and cutting-edge bioinformatics, it focuses on the interaction mechanism of the immune and nervous system and other tissue-specific microenvironments in the inflammatory response.
.
With the support of the National Overseas High-level Talents Program, the National Natural Science Foundation of China Joint Fund Key Project, and the Ministry of Science and Technology Key R&D Program, various projects in the laboratory are progressing smoothly.
There is an urgent need for young talents (postdoctoral, doctoral students, scientific research assistants).
Join us to grow and develop together! The research interest of He Danyang's research group at West Lake University is to explore the interaction mechanism between the immune and nervous systems
.
On the basis of organic integration of genetics, cell biology, and system biology, the immune regulation mechanism in neurodevelopment and disease will be systematically explored
.
It is hoped that the research results can contribute to a comprehensive understanding of neurodevelopmental regulatory networks and the discovery of new targets for the treatment of cognitive impairment and neurodegenerative diseases
.
The main research directions include: (1) exploring the functions and molecular mechanisms of microglia in neurodevelopment and nervous system diseases; (2) revealing the function of meningeal immunity in central nervous system homeostasis and inflammation; (3) systemic Map the molecular and cellular network of the intestinal glial immune circuit in intestinal homeostasis and inflammation
.
The laboratory currently has post-doctoral, doctoral and research assistant positions, welcome to contact us! Resume delivery (If you are interested, please send your resume and other materials to): https://jinshuju.
net/f/ZqXwZt or scan the QR code to deliver your resume.
Platemaker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article All, personal forwarding and sharing are welcome, reprinting is prohibited without permission, the author has all legal rights, and offenders must be investigated
.
