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, Ifor R. Williams, Rodney D. Newberry

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

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. HF 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 reduction 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.

Original languageEnglish
Pages (from-to)1229-1240
Number of pages12
JournalAmerican Journal of Pathology
Volume170
Issue number4
DOIs
StatePublished - Apr 2007

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