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(American Journal of Pathology. 2007;170:1229-1240.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060817

CC Chemokine Receptor 6 Expression by B Lymphocytes Is Essential for the Development of Isolated Lymphoid Follicles

Keely G. McDonald*, Jacquelyn S. McDonough*, Caihong Wang*, Torsten Kucharzik{dagger}, Ifor R. Williams{ddagger} and Rodney D. Newberry*

From the Department of Internal Medicine,* Washington University School of Medicine, St. Louis, Missouri; the Department of Medicine B,{dagger} University of Muenster, Muenster, Germany; and the Department of Pathology and Laboratory Medicine,{ddagger} Emory University School of Medicine, Atlanta, Georgia

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.








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Copyright © 2007 by the American Society for Investigative Pathology.