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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Candida albicans / immunology
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation / immunology*
  • Mycoses / immunology*

Substances

  • Cytokines