Dissertation

Structural Characteristics of Fat-Associated Lymphoid Tissues and their Role in the Peritoneal Propagation of B- Cell Lymphoma

Jia, Xinkai

2022

Overview

Following the entry of pathogens through skin or mucosal surfaces as first line of defense, during their propagation the pathogens are transported by various immune cells to the nearby secondary lymphoid organs, such as lymph nodes or Peyer's patches (1). Here, the lymphoid architecture allows for the efficient communication and cooperation between various leukocytes, despite their compartmentalization into different domains, including follicles (B-cell zones) and neighboring T-cell dominated regions. The recognition of antigens elicits different types of immune reactions, often resulting in the transformation of resting follicles into secondary follicles harboring germinal centers (2).Generally, secondary lymphoid organs, such as spleen, lymph nodes and programmed intestinal lymphoid tissues, including Peyer’s patches and mesenteric lymph nodes, start to develop before birth (3); however, there is another branch of the lymphoid structure that plays role in the local immunological challenges under the mucosa, such as cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Their development is initiated after birth (4), allowing the expanded immunological surveillance of the mucosal surface of the intestines, continuously exposed to alimentary and microbial antigens. In contrast to these well-studied lymphoid tissues, the role of serosa in the immune system has not been fully investigated. Although substantially lesser surface compared to the mucosal area, the serosa nevertheless represents a considerably large surface shared by various abdominal organs, often in a close arrangement with adipose tissue, and harboring a unique immunological compartment including a large number of B-1 B cells (5).Adipose tissue is usually considered as a vital energy storage. However, recent studies have unveiled the immunological potentials of adipose-associated lymphoid structures, which play essential roles in the local immune response (6–8), where they typically appear in diffuse forms and are embedded into the adipose components (9). Adipose tissue contains various lymphoid territories which participate in the local immunological challenge (6, 7). Visceral fat contains numerous leukocytes, which form adipose-associated lymphoid organoids. Here the focal accumulation of leukocytes is promoted by chemokines CXCL1 and CXCL13 (8).Typically they appear in diffuse forms and are embedded into the adipose (9). As prototypic adipose tissue containing lymphoid congregates, the omentum has been considered the main guardian in the abdominal cavity for a long time (10). The milky spots (MSs) on the surface of the omentum contain various leukocytes with an extensive capillary meshwork (11–13), where B-1 cells are the major source of natural antibodies (14). Even though there is no evidence of germinal centers or follicular dendritic cells (FDCs), T-dependent humoral immune responses can also occur in the MSs (15, 16). More recently, fat-associated lymphoid clusters (FALCs) were discovered in the mesenteric fat and at other visceral locations (17–19). They contain B cells, T cells, macrophages, and other innate lymphoid cells including ILC2, which promote B1 cell proliferation (17, 18). (Fig. 1).B cells are essential elements of adaptive immunity in the body. Eventually, they will secret antibodies and differentiate into plasma cells or long-lived memory B cells (20–23). Besides that, B cells are also able to regulate immune functions through cytokine production (24, 25). Following extensive research on their developmental and differentiation characteristics, B cells are now divided into several subsets according to the cell surface markers, transcription factor specifications and immunological functions. B-1 lymphocytes promote innate-like immune response typically with natural antibodies production, and B-2 cells with regulatory activities or antigen presentation, in addition to antigen recognition (26, 27). During these processes, various activation status-related and position-related (resting or activated; in follicles mantle zone or germinal center-located, or within germinal center, light zone or dark zone located, respectively) subsets can be distinguished. As two main products, either memory B cells or plasma cells may form. Importantly, the various lymphoid tissue locations confer distinct microenvironmental cues for B-cell subset survival and commitment, thus affecting the differentiation and specialization, including Ig isotype switch, short-term or long-term plasmablast differentiation.

• Publisher: ProQuest Dissertations & Theses
• Subject: Antibodies / Antigens / Biochemistry / Blood vessels / Body fat / Cells / Cellular biology / Chemokines / Clustering / Cytokines / Flow cytometry / Histology / Immunohistochemistry / Immunology / Leukocytes / Lymphocytes / Medical prognosis / Medicine / Mesentery / Metastasis / Oncology / Plasma / Software / Spleen / Tumors
• ISBN: 9798384328117