Human intestinal B cells in inflammatory diseases

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1. B cell responses in the human gut

장 내강에서는 병원체의 침입에 대하여 능동적으로 보호하기 위해 복잡한 균형을 이루고 있다. B cell은 장에서 이러한 보호를 위한 핵심적인 세포이다. B cell의 활성과 성숙은 신체에서 가장 큰 plasma cell 집단을 생성하는 등 여러 역할을 수행한다. GALT에서 생성된 Antibody-secreting plasma cell과 전구체는 lamina propria를 확산시키기 위해 광범위하게 퍼진다. GALT에서 IgG를 발현하는 memory B cell은 드물지 않지만, IgG를 분비하는 intestinal plasma cell은 흔하다. Gut IgG plasma cell은 염증성 장 질환에서 장 염증의 주요 원인이다.
2. Sampling lymphoid tissue in the human gut

인간의 GALT를 출생 전부터 노년까지 연구한 결과 출생 전에는 GALT가 구성적으로 존재하고 난포가 시간에 따라 점차적으로 감소하기 전에 12~18세까지 빈도가 증가하는 것을 보여주었다. GALT의 기억 Bcell은 IgM, IgA, IgG를 발현할 수 있으며, GALT에서 IgG를 발현하는 B cell은 GALT에서 germinal centre 반응에 참여할 수 있다.
3. Sites of induction and expression of B cell responses

항원이 들어오는 장내 환경은 결장에 있는 일부 여포들을 제외하고 GALT B세포 여포 내에 germinal centre의 ubiquitous 형성을 초래한다. 림프관에 GALT를 남기는 세포는 혈액으로 들어가고 GALT가 취약한 고유층을 보호하는 plasma cell과 effector T cell을 생성할 수 있기 때문에 중요하다.
4. T cell dependent on the B cell niche

GALT의 subsequent organization은 점막 및 전신 질환과 관련될 수 있는 T세포의 특정 하위집합의 발달을 초래한다. T follicular helper cell과 T follicular regulatory cell은 CXXR5를 발현할 때 germinal centre로 들어가는 경향이 있고, T follicular helper cell은 B 세포 반응에 대한 도움을 제공하고, T follicular regulatory cell은 T follicultar helper cell을 negative하게 조절한다.
5. Lymphoid structures in Inflammatory Bowel Disease(IBD)

IBD와 비장 기능저하가 있는 환자는 순환하는 비정상적인 적혈구에 의해 결정되며 건강한 사람에 비해 혈액 내 CD27+IgM+B 세포의 빈도가 감소한다. 궤양성 대장염 또는 크론병 환자의 말초혈액은 건강한 혈액과 비교했을 때, 다른 모든 이소형을 발현하는 CD27-IgD- memory B cell이 고갈된다.
6. Repertoire of intestinal plasma cells

건강에 있어서 장내 점막을 보호하는 IgA plasma cell 집단은 체내에서 가장 큰 형질 세포 집단이다. 대부분의 인간 장내 IgA는 여러 박테리아 분류군에 의해 발현될 수 있는 에피토프에 특이적이며, 공유 에피토프에 매우 특이적임에도 불구하고 다중 특이성을 나타낸다.
7. B cell repertoire in intestinal inflammation

궤양성 대장염 환자에서 전체에서 차지하는 IgG 분비 형질 세포의 빈도는 크론병 환자보다 높다. 궤양성 대장염 환자의 B 세포 및 형질 세포 레퍼토리에 대한 심층 단일 세포 분석에서 JH6 과 관련된 재배열에 대한 편향이 확인되었으며, 체세포 초돌연변이의 빈도는 IgA 생성 및 IgG 생성에서 더 낮다.

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1. B cell responses in the human gut

The human gut is a complex and dynamic environment that plays a crucial role in the body's immune response. B cells, a type of white blood cell, are an integral part of this immune system, responsible for producing antibodies that help protect the body from harmful pathogens. Understanding the B cell responses in the human gut is essential for developing effective treatments and therapies for various gastrointestinal disorders. The gut-associated lymphoid tissue (GALT) is the primary site of B cell responses in the human gut. GALT is composed of organized lymphoid structures, such as Peyer's patches and isolated lymphoid follicles, which serve as induction sites for B cell activation and differentiation. These structures provide a specialized microenvironment that supports the development and maturation of B cells, enabling them to mount effective immune responses against invading pathogens. B cells in the gut can undergo class-switching and somatic hypermutation, processes that allow them to produce a diverse repertoire of antibodies with increased affinity and specificity. This diversity is crucial for the gut's ability to respond to a wide range of antigens, including those from commensal microbiota and dietary components, as well as pathogens. The regulation of B cell responses in the gut is a complex and tightly controlled process, involving various cytokines, chemokines, and cell-cell interactions. Understanding the mechanisms that govern these responses is essential for developing targeted therapies that can modulate B cell function in the context of gastrointestinal diseases, such as inflammatory bowel disease (IBD) and food allergies.
2. Sampling lymphoid tissue in the human gut

Sampling lymphoid tissue in the human gut is a crucial aspect of understanding the immune responses that occur within this complex and dynamic environment. The gut-associated lymphoid tissue (GALT) is a specialized collection of organized lymphoid structures, including Peyer's patches, isolated lymphoid follicles, and mesenteric lymph nodes, that play a central role in the induction and regulation of immune responses. Accurate and representative sampling of these lymphoid tissues is essential for gaining insights into the cellular and molecular mechanisms that underlie gut immunity. This can be achieved through various techniques, such as endoscopic biopsies, surgical resections, and even minimally invasive methods like capsule endoscopy. The challenges associated with sampling lymphoid tissue in the gut include the heterogeneity of the tissue, the potential for sampling bias, and the need to preserve the delicate microenvironment. Careful consideration must be given to the timing, location, and method of sampling to ensure that the obtained samples are representative and can provide meaningful insights into the complex interplay between the gut microbiome, the immune system, and various disease states. Advances in imaging technologies, such as high-resolution endoscopy and intravital microscopy, have also enabled researchers to study the dynamic interactions within the gut lymphoid tissue in real-time, further enhancing our understanding of the gut immune system. By combining these sampling techniques with advanced analytical methods, such as single-cell sequencing and high-dimensional flow cytometry, researchers can gain a more comprehensive understanding of the B cell responses and other immune processes occurring within the human gut.
3. Sites of induction and expression of B cell responses

The induction and expression of B cell responses in the human gut occur within specialized lymphoid structures and microenvironments. Understanding the specific sites where these processes take place is crucial for elucidating the mechanisms underlying gut immunity and developing targeted therapies for gastrointestinal disorders. The primary sites of B cell induction in the gut are the organized lymphoid structures known as Peyer's patches and isolated lymphoid follicles. These structures serve as induction sites, where B cells encounter antigens, undergo activation, and initiate the process of differentiation and maturation. Within these specialized microenvironments, B cells interact with other immune cells, such as T cells and dendritic cells, which provide the necessary signals and support for their development. Once activated and differentiated, B cells can migrate to various sites within the gut to express their effector functions. These sites include the lamina propria, the mucosal layer of the intestine, where plasma cells secrete antibodies that provide local protection against pathogens. Additionally, B cells can also home to the mesenteric lymph nodes, where they can further interact with T cells and contribute to the systemic immune response. The regulation of B cell responses in the gut is a complex and dynamic process, involving various chemokines, cytokines, and cell-cell interactions. Understanding the specific sites of induction and expression of B cell responses, as well as the factors that govern these processes, is crucial for developing targeted therapies that can modulate B cell function in the context of gastrointestinal diseases, such as inflammatory bowel disease (IBD) and food allergies.
4. T cell dependent on the B cell niche

The relationship between T cells and the B cell niche in the human gut is a critical aspect of gut immunity. T cells play a crucial role in the regulation and support of B cell responses, and the specialized microenvironment, or niche, within the gut-associated lymphoid tissue (GALT) is essential for the development and function of both cell types. The B cell niche in the gut is characterized by the organized lymphoid structures, such as Peyer's patches and isolated lymphoid follicles, which provide a specialized microenvironment for B cell activation, differentiation, and maturation. Within these structures, B cells interact with various cell types, including T cells, dendritic cells, and stromal cells, which provide the necessary signals and support for their development. T cells, particularly T follicular helper (Tfh) cells, play a crucial role in the B cell niche by providing essential signals for B cell activation, class-switching, and the generation of high-affinity antibodies. Tfh cells, which reside within the germinal centers of the GALT, secrete cytokines and express surface molecules that promote the proliferation, differentiation, and survival of B cells. Conversely, the B cell niche also supports the development and function of T cells. The specialized microenvironment within the GALT, with its unique antigen-presenting cells and cytokine milieu, can influence the differentiation and function of T cells, including their ability to provide help to B cells. Understanding the intricate relationship between T cells and the B cell niche in the gut is crucial for developing targeted therapies that can modulate immune responses in the context of gastrointestinal diseases, such as inflammatory bowel disease (IBD) and food allergies. By targeting the specific interactions and signaling pathways within the B cell niche, it may be possible to enhance or suppress B cell responses as needed, leading to improved clinical outcomes for patients.
5. Lymphoid structures in Inflammatory Bowel Disease(IBD)

Inflammatory Bowel Disease (IBD), which encompasses conditions like Crohn's disease and ulcerative colitis, is a chronic and debilitating gastrointestinal disorder characterized by inflammation of the gut. The role of lymphoid structures in the pathogenesis and progression of IBD is a crucial area of research, as these specialized immune compartments play a central role in the regulation of gut immunity. In IBD, the gut-associated lymphoid tissue (GALT), which includes Peyer's patches, isolated lymphoid follicles, and mesenteric lymph nodes, undergoes significant structural and functional changes. These alterations can contribute to the dysregulation of the immune response, leading to the chronic inflammation and tissue damage observed in IBD patients. One of the hallmarks of IBD is the increased formation of ectopic lymphoid structures, also known as tertiary lymphoid organs, within the inflamed intestinal mucosa. These structures, which resemble the organized lymphoid tissue found in the GALT, can serve as additional sites for the induction and perpetuation of the immune response, further exacerbating the inflammatory process. The presence and characteristics of these lymphoid structures in IBD can provide valuable insights into the underlying pathogenic mechanisms. For example, the composition and organization of the immune cells within these structures, as well as the expression of specific cytokines and chemokines, can shed light on the dysregulation of the gut immune system in IBD. Understanding the role of lymphoid structures in IBD is crucial for the development of targeted therapies that can modulate the immune response and restore the balance within the gut. By targeting the specific pathways and interactions within these specialized immune compartments, it may be possible to dampen the chronic inflammation and promote the resolution of the disease process. Overall, the study of lymphoid structures in IBD is a promising area of research that can contribute to a deeper understanding of the complex interplay between the immune system and the gut, ultimately leading to improved clinical management and outcomes for patients with this debilitating condition.
6. Repertoire of intestinal plasma cells

The repertoire of intestinal plasma cells is a crucial aspect of gut immunity, as these specialized antibody-producing cells play a central role in the local and systemic immune response. Understanding the diversity and characteristics of the intestinal plasma cell repertoire can provide valuable insights into the mechanisms underlying the maintenance of gut homeostasis and the development of gastrointestinal diseases. Intestinal plasma cells are derived from B cells that have undergone activation, differentiation, and class-switching within the gut-associated lymphoid tissue (GALT), such as Peyer's patches and isolated lymphoid follicles. These plasma cells secrete a diverse array of antibodies, including IgA, IgG, and IgM, which are essential for protecting the gut from harmful pathogens and maintaining the delicate balance between the host and the commensal microbiota. The repertoire of intestinal plasma cells is shaped by various factors, including the exposure to dietary and microbial antigens, the interactions with other immune cells, and the local cytokine and chemokine milieu. This repertoire is highly dynamic and can undergo significant changes in response to environmental and physiological cues, such as changes in the gut microbiome or the development of gastrointestinal diseases. Alterations in the intestinal plasma cell repertoire have been observed in various gastrointestinal disorders, including inflammatory bowel disease (IBD), celiac disease, and food allergies. These changes can reflect the dysregulation of the gut immune system and may contribute to the pathogenesis and progression of these conditions. By studying the repertoire of intestinal plasma cells, researchers can gain insights into the specific antibody responses that are involved in the maintenance of gut homeostasis and the development of gastrointestinal diseases. This knowledge can inform the development of targeted therapies that aim to modulate the plasma cell response and restore the balance within the gut, potentially leading to improved clinical outcomes for patients with these conditions.
7. B cell repertoire in intestinal inflammation

The B cell repertoire in the context of intestinal inflammation is a crucial aspect of gut immunity, as B cells play a central role in the immune response and the maintenance of gut homeostasis. Understanding the dynamics and characteristics of the B cell repertoire in the inflamed gut can provide valuable insights into the pathogenesis and progression of gastrointestinal diseases. During intestinal inflammation, the gut-associated lymphoid tissue (GALT), which includes Peyer's patches, isolated lymphoid follicles, and mesenteric lymph nodes, undergoes significant changes in the composition and function of B cells. These changes can lead to the expansion of specific B cell clones, the generation of high-affinity antibodies, and the altered homing and trafficking of B cells within the gut. The B cell repertoire in the inflamed gut is shaped by various factors, including the exposure to microbial and dietary antigens, the interactions with other immune cells (such as T cells and dendritic cells), and the local cytokine and chemokine milieu. These factors can influence the activation, differentiation, and maturation of B cells, leading to the generation of a diverse repertoire of antibodies that can target specific pathogens or contribute to the perpetuation of the inflammatory response. Alterations in the B cell repertoire have been observed in various gastrointestinal disorders, such as inflammatory bowel disease (IBD), celiac disease, and food allergies. These changes can reflect the dysregulation of the gut immune system and may contribute to the pathogenesis and progression of these conditions. By studying the B cell repertoire in the context of intestinal inflammation, researchers can gain insights into the specific antibody responses that are involved in the development and maintenance of gastrointestinal diseases. This knowledge can inform the development of targeted therapies that aim to modulate the B cell response and restore the balance within the gut, potentially leading to improved clinical outcomes for patients with these conditions.

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