4.6 Article

CCR6-Dependent Positioning of Memory B Cells Is Essential for Their Ability To Mount a Recall Response to Antigen

Journal

JOURNAL OF IMMUNOLOGY
Volume 194, Issue 2, Pages 505-513

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1401553

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Funding

  1. National Institutes of Health [R37AI26296]
  2. Merck grant
  3. Medical Research Council (U.K.) [G0802068]
  4. Wellcome Trust [WT088747MA]
  5. British Heart Foundation [PG/12/36/29444]
  6. National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas' National Health Service (NHS) Foundation Trust and King's College London
  7. MRC [G0802651, G108/380, G0802068] Funding Source: UKRI
  8. British Heart Foundation [PG/12/36/29444] Funding Source: researchfish
  9. Medical Research Council [MR/K500999/1, G0802651, G108/380, G0802068] Funding Source: researchfish

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Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B-mem) are essential for the secondary humoral immune responses, the chemokine response patterns of B-mem cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B-mem cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B-mem, CCR6 is essential for the ability of B-mem to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B-mem was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B-mem from the marginal and perifollicular to the follicular/germinal center area.

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