Lymphoid organ development: from ontogeny to neogenesis

Abstract

The development of lymphoid organs can be viewed as a continuum. At one end are the 'canonical' secondary lymphoid organs, including lymph nodes and spleen; at the other end are 'ectopic' or tertiary lymphoid organs, which are cellular accumulations arising during chronic inflammation by the process of lymphoid neogenesis. Secondary lymphoid organs are genetically 'preprogrammed' and 'prepatterned' during ontogeny, whereas tertiary lymphoid organs arise under environmental influences and are not restricted to specific developmental 'windows' or anatomic locations. Between these two boundaries are other types of lymphoid tissues that are less developmentally but more environmentally regulated, such as Peyer's patches, nasal-associated lymphoid tissue, bronchial-associated lymphoid tissue and inducible bronchial-associated lymphoid tissue. Their regulation, functions and potential effects are discussed here.

Progression of carcinogen‐induced fibrosarcomas is associated with the accumulation of naïve CD4+ T cells via blood vessels and lymphatics

“…HEVs are specialized blood vessels, which, under nonpathological conditions, are found only in secondary lymphoid organs where they allow naïve T‐cell entry (reviewed in Ref. 13). As we have reported previously, however, HEVs are not found in unmanipulated MCA‐induced fibrosarcomas and thus cannot account for the enrichment of naïve T cells in these tumors 14…”

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

“…Consequently, lymphoid organs share a cellular organization that includes a germinal centre comprising antibody secreting and proliferating B cells together with follicular dendritic cells (DCs); a T‐cell zone including naive cells recruited from the blood; high endothelial venules (HEV) for lymphocyte extravasation; and a network of stromal cells that provide chemokines and extracellular matrix for cellular migration and structural integrity 1, 3…”

“…Likewise, as some tissues and tumours are more permissive to ELF development than others, the tissue microenvironment must contribute defined signals that are conducive to lymphoid neogenesis. In this regard, the development of ELFs mimics many of the mechanisms underpinning the organogenesis of SLOs (for a comprehensive review of SLO development see refs 1, 12). Here, initiation of SLO development centres on an interaction at the lymph node anlagen between haematopoietic derived CD4 + CD45 + CD3 − LTi cells and lymphoid tissue organizer (LTo) cells of mesenchymal origin.…”

“…The expression of homeostatic chemokines is increased in tissues where ELFs have emerged in response to foreign or auto antigens 1, 9, 10, 12. Chemokines such as CXCL13, CCL19, CCL21 and CXCL12 are involved not only in the initiation of ELF development, but also in the maintenance of the highly organized cellular architecture of established ELFs and SLOs.…”

The unexpected role of lymphotoxin β receptor signaling in carcinogenesis: from lymphoid tissue formation to liver and prostate cancer development

“…The role of LT in the context of lymphoid neogenesis, development of autoimmune diseases and inflammatory disorders was further investigated in vivo (Picarella et al, 1992;Kratz et al, 1996;Luther et al, 2000;Drayton et al, 2003Drayton et al, , 2006Gommerman and Browning, 2003;Martin et al, 2004;Heikenwalder et al, 2005Heikenwalder et al, , 2008Haybaeck et al, 2009). These studies revealed that ectopic LT expression suffices to generate lymphoid-like structures (Picarella et al, 1992;Kratz et al, 1996;Gommerman and Browning, 2003;Heikenwalder et al, 2005;Haybaeck et al, 2009), also termed tertiary lymphoid organs or tissues.…”