title: The skin, a novel niche for recirculating B cells.
abstract: B cells infiltrate the skin in many chronic inflammatory diseases caused by autoimmunity or infection. Despite potential contribution to disease, skin-associated B cells remain poorly characterized. Using an ovine model of granulomatous skin inflammation, we demonstrate that B cells increase in the skin and skin-draining afferent lymph during inflammation. Surprisingly, skin B cells are a heterogeneous population that is distinct from lymph node B cells, with more large lymphocytes as well as B-1-like B cells that coexpress high levels of IgM and CD11b. Skin B cells have increased MHC class II, CD1, and CD80/86 expression compared with lymph node B cells, suggesting that they are well-suited for T cell activation at the site of inflammation. Furthermore, we show that skin accumulation of B cells and Ab-secreting cells during inflammation increases local Ab titers, which could augment host defense and autoimmunity. Although skin B cells express typical skin-homing receptors, such as E-selectin ligand and α-4 and β-1 integrins, they are unresponsive to ligands for chemokine receptors associated with T cell homing into skin. Instead, skin B cells migrate toward the cutaneously expressed CCR6 ligand CCL20. Our data support a model in which B cells use CCR6-CCL20 to recirculate through the skin, fulfilling a novel role in skin immunity and inflammation.
authors.affiliation: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
authors.forename: Skye A
authors.initials: SA
authors.lastname: Geherin
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Fintushel
authors.forename: Michael H
authors.initials: MH
authors.lastname: Lee
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wilson
authors.forename: Reema T
authors.initials: RT
authors.lastname: Patel
authors.forename: Carsten
authors.initials: C
authors.lastname: Alt
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Young
authors.forename: John B
authors.initials: JB
authors.lastname: Hay
authors.forename: Gudrun F
authors.initials: GF
authors.lastname: Debes
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D012756:Sheep; D012867:Skin / Q000166:cytology* / Q000276:immunology*
chemical_list: D019707:Receptors, Chemokine