CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles.
Isolated lymphoid follicles (ILFs) are organized lymphoid structures that facilitate the efficient interaction of antigen, antigen-presenting cells, and lymphocytes to generate controlled adaptive immune responses within the intestine. Because CC chemokine receptor 6 (CCR6) deficiency affects the generation of mucosal immune responses, we evaluated a potential role for CCR6 in the development of ILFs. We observed that CCR6 and its ligand CCL20 are highly expressed within ILFs and that B lymphocytes are the largest CCR6-expressing population within ILFs. ILF development was profoundly arrested in the absence of CCR6. Concordant with a block in ILF development at a stage corresponding to the influx of B lymphocytes, we observed that CCR6-deficient mice had a diminished population of intestinal B lymphocytes. Bone marrow reconstitution studies demonstrated that ILF development is dependent on CCR6-sufficient B lymphocytes, and adoptive transfers demonstrated that CCR6(-/-) B lymphocytes were inefficient at localizing to intestinal lymphoid structures. Paralleling these findings, we observed that CCR6-deficient mice had a reduced proportion of Peyer's patch B lymphocytes and an associated re-duction in the number and size of Peyer's patch follicular domes. These observations define an essential role for CCR6 expression by B lymphocytes in localizing to intestinal lymphoid structures and in ILF development.
McDonald
Keely G
KG
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
McDonough
Jacquelyn S
JS
Wang
Caihong
C
Kucharzik
Torsten
T
Williams
Ifor R
IR
Newberry
Rodney D
RD
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000378:metabolism; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000254:growth & development / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010581:Peyer's Patches / Q000254:growth & development / Q000378:metabolism*; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000378:metabolism
C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D018800:Thy-1 Antigens