title: Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses.
abstract: Fungal infections (e.g.,Candida albicans) can manifest as serious medical illnesses, especially in the elderly and immune-compromised hosts. T cells are important forCandidacontrol. Whether and how B cells are involved in antifungal immunity has been less clear. Although patients with agammaglobulinemia exhibit normal antifungal immunity, increased fungal infections are reported following B cell-depleting therapy, together pointing to Ab-independent roles of B cells in controlling such infections. To test how human B cells may contribute to fungal-associated human T cell responses, we developed a novel Ag-specific human T cell/B cell in vitro coculture system and found that human B cells could induceC. albicans-associated, MHC class II-restricted responses of naive T cells. Activated B cells significantly enhancedC. albicans-mediated Th1 and Th17 T cell responses, which were both strongly induced by CD80/CD86 costimulation. IL-6+GM-CSF+B cells were the major responding B cell subpopulation toC. albicansand provided efficient costimulatory signals to the T cells. In vivo B cell depletion in humans resulted in reducedC. albicans-associated T responses. Of note, the decreased Th17, but not Th1, responses could be reversed by soluble factors from B cells prior to depletion, in an IL-6-dependent manner. Taken together, our results implicate an Ab-independent cytokine-defined B cell role in human antifungal T cell responses. These findings may be particularly relevant given the prospects of chronic B cell depletion therapy use in lymphoma and autoimmune disease, as patients age and are exposed to serial combination therapies.
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.|Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.|Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Ayman
authors.initials: A
authors.lastname: Rezk
authors.affiliation: Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gommerman
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame, Montreal, Quebec H2L 4M1, Canada; and.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada; amitbar@upenn.edu.|Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.|Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D009181:Mycoses / Q000276:immunology*
chemical_list: D016207:Cytokines