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

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

H S Carlsen1,
E S Baekkevold2,
F-E Johansen2,
G Haraldsen2,
P Brandtzaeg2
1Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, and Department of Surgery, University of Oslo, Rikshospitalet, Oslo, Norway
2Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet, Oslo, Norway
Correspondence to:
H S Carlsen, LIIPAT, Institute of Pathology, Rikshospitalet, N-0027 Oslo, Norway;
hege.carlsen{at}klinmed.uio.no

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.

gut associated lymphoid tissue
ulcerative colitis
inflammatory bowel disease
B cell attracting chemokine 1
CXC chemokine receptor 5
BCA-1, B cell attracting chemokine (in humans)
BLA, basal lymphoid aggregate
BLC, B lymphocyte chemoattractant (in mice)
CXCL13, CXC chemokine ligand 13
CXCR5, CXC chemokine receptor 5
DIG, digoxigenin
DRC, dendritic reticulum cell
FDC, follicular dendritic cell
GALT, gut associated lymphoid tissue
GAPDH, glyceraldehyde-3-phosphate dehydrogenase
GC-Th, germinal centre T helper
H&E, haematoxylin and eosin
IBD, inflammatory bowel disease
MAdCAM-1, mucosal addressin cell adhesion molecule 1
MALT, mucosa associated lymphoid tissue
PP, Peyer's patch
RT-PCR, reverse transcription-polymerase chain reaction
vWF, von Willebrandt factor
UC, ulcerative colitis

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