title: CD11c-Expressing B Cells Are Located at the T Cell/B Cell Border in Spleen and Are Potent APCs.
abstract: In addition to the secretion of Ag-specific Abs, B cells may play an important role in the generation of immune responses by efficiently presenting Ag to T cells. We and other investigators recently described a subpopulation of CD11c(+) B cells (Age/autoimmune-associated B cells [ABCs]) that appear with age, during virus infections, and at the onset of some autoimmune diseases and participate in autoimmune responses by secreting autoantibodies. In this study, we assessed the ability of these cells to present Ag and activate Ag-specific T cells. We demonstrated that ABCs present Ag to T cells, in vitro and in vivo, better than do follicular B cells (FO cells). Our data indicate that ABCs express higher levels of the chemokine receptor CCR7, have higher responsiveness to CCL21 and CCL19 than do FO cells, and are localized at the T/B cell border in spleen. Using multiphoton microscopy, we show that, in vivo, CD11c(+) B cells form significantly more stable interactions with T cells than do FO cells. Together, these data identify a previously undescribed role for ABCs as potent APCs and suggest another potential mechanism by which these cells can influence immune responses and/or the development of autoimmunity.
authors.affiliation: Howard Hughes Medical Institute, Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Denver, Anschutz Medical Campus, Denver, CO 80206; rubtsova@njhealth.org marrackp@njhealth.org.
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Rubtsov
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver, Anschutz Medical Campus, Denver, CO 80206;
authors.forename: Kira
authors.initials: K
authors.lastname: Rubtsova
authors.affiliation: Howard Hughes Medical Institute, Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Denver, Anschutz Medical Campus, Denver, CO 80206; Department of Pharmacology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045; and.
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver, Anschutz Medical Campus, Denver, CO 80206;
authors.forename: Jordan
authors.initials: J
authors.lastname: Jacobelli
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver, Anschutz Medical Campus, Denver, CO 80206;
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Friedman
authors.affiliation: Howard Hughes Medical Institute, Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Denver, Anschutz Medical Campus, Denver, CO 80206; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045; and Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045 rubtsova@njhealth.org marrackp@njhealth.org.
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D054415:Chemokine CCL19 / Q000235:genetics / Q000276:immunology; D054421:Chemokine CCL21 / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D001323:Autoantibodies; D039521:CD11c Antigen; C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054400:Receptors, CCR7