The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity

Abstract

The development of secondary lymphoid organs is a complex process dependent on a coordinated interaction of cells of hematopoietic and non-hematopoietic origin. In this context, chemokines and cytokines belonging to the tumor necrosis factor (TNF)/lymphotoxin (LT) family are critical signaling molecules during the initial steps of lymph node and Peyer's patch organogenesis. Homeostatic chemokines, such as CXCL13, CCL21, and CCL19, as well as their corresponding receptors, CXCR5 and CCR7, have now been shown to closely cooperate in the development of lymphoid organs and the maintenance of lymphoid tissue microarchitecture. We summarize recent data on the function of CXCR5 and CCR7 and their intricate connection to the TNF/LT system in order to refine the current model of lymphoid organ development.

B Lymphocyte Autoimmunity in Rheumatoid Synovitis Is Independent of Ectopic Lymphoid Neogenesis

“…Taken together with the coexistence of different degrees of lymphoid organization in a single sample (23,26), these data indicate that synovial lymphoid neogenesis is a dynamic process which could be related to inflammation rather than a fixed pathological feature committed to specific B cell autoantigens. In SLO, Ag-driven B cell responses require the full maturation of lymphoid structures toward GC-reactions, a complex process orchestrated by lymphoid chemokines and cytokines (49,50) Defective expression of these mediators leads to abortive follicle formation and impaired B cell responses (49,51). The overexpression of these cytokines in RA synovial lymphoid neogenesis suggests that they could have a similar function in synovial tissue and thus that full maturation toward GC-reactions may be more relevant to B cell autoimmune responses than the mere presence of large lymphoid aggregates (15,23).…”

CXCR5+ CCR7– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

“…One approach to analyse a T cell response is to examine the expression of receptors that mediate homing of T cells, such as CD62L, which binds to glycosylation-dependent cell adhesion molecule 1 on [4,20,21]. CXCR5 is a chemokine receptor which is expressed on all B cells and on specialized subsets of DC and T cells [22]. It has only one known ligand, the chemokine CXCL13, mainly produced by stromal cells and follicular DC within B cell follicles [23][24][25].…”

“…CXCR5 is a chemokine receptor which is expressed on all B cells and on specialized subsets of DC and T cells [22]. It has only one known ligand, the chemokine CXCL13, mainly produced by stromal cells and follicular DC within B cell follicles [23][24][25].…”

CXC Chemokine Ligand 13 and CC Chemokine Ligand 19 Cooperatively Render Resistance to Apoptosis in B Cell Lineage Acute and Chronic Lymphocytic Leukemia CD23+CD5+ B Cells

“…Homeostatic chemokines, such as CXCL13, CCL21, and CCL19, as well as their corresponding receptors, CXCR5 and CCR7, have been shown to closely cooperate in the development of lymphoid organs and the maintenance of lymphoid tissue microarchitecture (2). Expression of CXCR5 can be detected on mature recirculating B cells, small subsets of normal CD4 ϩ and CD8 ϩ T cells, and skin-derived migratory dendritic cells (3)(4)(5)(6).…”

“…CCL19 (EBV-induced gene-1 ligand chemokine (ELC)) and CCL21 (secondary lymphoid tissue chemokine/6Ckine) are ligands for the chemokine receptor CCR7 (Burkitt lymphoma receptor-2), whereas CXCL13 (B cell-attracting chemokine 1 (BCA-1)) is the only ligand for CXCR5 (Burkitt lymphoma receptor-1) (2). Homeostatic chemokines, such as CXCL13, CCL21, and CCL19, as well as their corresponding receptors, CXCR5 and CCR7, have been shown to closely cooperate in the development of lymphoid organs and the maintenance of lymphoid tissue microarchitecture (2).…”