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J Immunol. 2017 Apr 15;198(8):3245-3254. doi: 10.4049/jimmunol.1601572. Epub 2017 Mar 8.

Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses.

Author information

1
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
2
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
3
Department of Neurobiology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
4
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
5
Centre de Recherche du Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame, Montreal, Quebec H2L 4M1, Canada; and.
6
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada; amitbar@upenn.edu.
7
Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.

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 for Candida control. 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 induce C. albicans-associated, MHC class II-restricted responses of naive T cells. Activated B cells significantly enhanced C. 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 to C. albicans and provided efficient costimulatory signals to the T cells. In vivo B cell depletion in humans resulted in reduced C. 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.

PMID:
28275140
DOI:
10.4049/jimmunol.1601572
[Indexed for MEDLINE]
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