title: Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c⁺ B-cell population is important for the development of autoimmunity.
abstract: Females are more susceptible than males to many autoimmune diseases. The processes causing this phenomenon are incompletely understood. Here, we demonstrate that aged female mice acquire a previously uncharacterized population of B cells that we call age-associated B cells (ABCs) and that these cells express integrin α(X) chain (CD11c). This unexpected population also appears in young lupus-prone mice. On stimulation, CD11c(+) B cells, both from autoimmune-prone and healthy strains of mice, secrete autoantibodies, and depletion of these cells in vivo leads to reduction of autoreactive antibodies, suggesting that the cells might have a direct role in the development of autoimmunity. We have explored factors that contribute to appearance of ABCs and demonstrated that signaling through Toll-like receptor 7 is crucial for development of this B cell population. We were able to detect a similar population of B cells in the peripheral blood of some elderly women with autoimmune disease, suggesting that there may be parallels between the creation of ABC-like cells between mice and humans.
authors.affiliation: Howard Hughes Medical Institute and Department of Immunology, National Jewish Health and University of Colorado Health Sciences Center, Denver, CO 80206, USA. rubtsova@njhealth.org
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Rubtsov
authors.forename: Kira
authors.initials: K
authors.lastname: Rubtsova
authors.forename: Aryeh
authors.initials: A
authors.lastname: Fischer
authors.forename: Richard T
authors.initials: RT
authors.lastname: Meehan
authors.forename: Joann Z
authors.initials: JZ
authors.lastname: Gillis
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
mesh_terms: D000368:Aged; D000375:Aging / Q000276:immunology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D039521:CD11c Antigen / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051199:Toll-Like Receptor 7 / Q000378:metabolism / Q000502:physiology*
chemical_list: D039521:CD11c Antigen; D051199:Toll-Like Receptor 7