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

• Published in: The Journal of immunology (1950) 2017-04, Vol.198 (8), p.3245-3254
• Main Authors: Li, Rui, Rezk, Ayman, Li, Hulun, Gommerman, Jennifer L, Prat, Alexandre, Bar-Or, Amit
• Format: Article
• Language: English
• Subjects: Agammaglobulinemia; Antifungal agents; B-Lymphocytes - immunology; Candida albicans; Candida albicans - immunology; CD4-Positive T-Lymphocytes - immunology; CD80 antigen; CD86 antigen; Coculture Techniques; Cytokines - biosynthesis; Cytokines - immunology; Depletion; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Fungal infections; Fungi; Fungicides; Geriatrics; Granulocyte-macrophage colony-stimulating factor; Helper cells; Human behavior; Humans; Infections; Interleukin 6; Lymphocyte Activation - immunology; Lymphocyte receptors; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Major histocompatibility complex; Mycoses - immunology; Older people; T cell receptors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601572

Fungal infections (e.g., ) can manifest as serious medical illnesses, especially in the elderly and immune-compromised hosts. T cells are important for 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 associated, MHC class II-restricted responses of naive T cells. Activated B cells significantly enhanced 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 and provided efficient costimulatory signals to the T cells. In vivo B cell depletion in humans resulted in reduced -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.