B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue

Abstract

Background and aims: In mice, the B lymphocyte chemoattractant (BLC) CXC chemokine ligand 13 (CXCL13) is sufficient to induce a series of events leading to the formation of organised lymphoid tissue. Its receptor, CXCR5, is required for normal development of secondary lymphoid tissue. However, the human counterpart, B cell attracting chemokine 1 (BCA-1) has only been detected in the stomach and appendix and not in other parts of normal or diseased gut. Hence to elucidate the potential role of this chemokine and its receptor in human gut associated lymphoid tissue (GALT), we analysed their expression in normal intestine and ulcerative colitis (UC). Methods: Frozen sections of surgical specimens were studied by multicolour immunofluorescence staining, in situ mRNA hybridisation, and reverse transcription-polymerase chain reaction. Results: BCA-1 mRNA was detected in all normal colonic and UC specimens. BCA-1 was produced and accumulated in relation to peripheral dendritic elements of lymphoid follicles in Peyer's patches and normal colon, as well as in irregular lymphoid aggregates in UC lesions. BCA-1 was partially associated with the traditional follicular dendritic cell phenotype but also with extracellular fibrils in GALT structures. CXCR5 protein was expressed by mantle zone B cells and appeared at a high level on scattered germinal centre T cells. Conclusions: BCA-1 and CXCR5 are expressed in normal GALT structures as well as in irregular lymphoid aggregates in UC. This strongly suggests that BCA-1 plays an important role not only in the formation of normal GALT but also in the generation of aberrant lymphoid tissue in inflammatory bowel disease.

Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis

“…3O-Q for structure and R, S for CXCL13). This localization is in keeping with previous studies showing CXCL13 production both in GC as well as in the B cell mantle zone in secondary lymphoid organs [24][25][26] and provide evidence of a similarity in the expression pattern of CXCL13 between secondary lymphoid organs and synovial lymphoid tissue.…”

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases

“…In salivary gland tissue from Sjogren's syndrome patients, CXCL13 was expressed within lymphoid aggregates that shared many structural features with normal GCs (11,33). CXCL13 is produced and accumulated in irregular lymphoid aggregates in ulcerative colitis lesions (12) and in Helicobacter pylori-induced, mucosal-associated lymphoid tissue and gastric lymphoma (34). CXCL13 and tumor necrosis factor family member lymphotoxin-b are both strongly involved in GC formation, and have been described as predictors for the recruitment of follicular dendritic cells and the formations of GCs in rheumatoid arthritis (9,10,35).…”

“…Here, they recapitulate the structure of normal secondary follicles. Ectopic lymphoid follicles have been demonstrated in synovium from chronic arthritis patients (9,10), in the salivary gland from patients with Sjogren's syndrome (11), and in intestinal specimens from patients with colitis ulcerosa (12). CXCL13 and CXCR5 are expressed in these irregular aggregates, suggesting that both may play a role in aberrant lymphoid tissue.…”

Lymphotoxin and TNF Produced by B Cells Are Dispensable for Maintenance of the Follicle-Associated Epithelium but Are Required for Development of Lymphoid Follicles in the Peyer’s Patches

“…Biochemical inhibition of LT␤R and TNFR signaling has been shown to be a promising therapeutic approach in mouse models of inflammatory bowel disease and experimental colitis (33,34). It remains to be determined whether such effects of LT␤R or TNFR blockers are linked to inhibition of BLC function in the areas of local inflammation in the gut where ectopic expression of BLC has been shown (35,36).…”