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

作者：Li, Rui; Rezk, Ayman; Li, Hulun; Gommerman, Jennifer L.; Prat, Alexandre; Bar-Or, Amit^*

来源：The Journal of Immunology, 2017, 198(8): 3245-3254.

DOI：10.4049/jimmunol.1601572

• ANTIGEN-PRESENTING CELLS
• PNEUMOCYSTIS-JIROVECI PNEUMONIA
• CANDIDA-ALBICANS
• HOST-DEFENSE
• TH17 CELLS
• RITUXIMAB TREATMENT
• UNITED-STATES
• IN-VIVO
• INFECTION
• IMMUNITY

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.

• 出版日期2017-4-15
• 单位McGill; 哈尔滨医科大学