Surface display of proteins on bone marrow-derived dendritic cells induces humoral immune responses and anaphylaxis

Abstract

While the presentation of peptides on major histocompatibility (MHC) molecules by dendritic cells (DCs) for T cell activation has been extensively documented, it has been unclear if DCs express surface receptors that can selectively exhibit unprocessed proteins for extended periods of time for recognition by B cells. We show here that murine bone marrow-derived DCs (BMDCs) incubated with serum proteins displayed these proteins on their surface and, when injected into recipient mice, induced the production of protein-specific antibodies. Subsequent challenge of BMDC-vaccinated recipient mice with these same serum proteins triggered severe anaphylaxis. Antigen-specific IgE was not necessary to mediate severe anaphylaxis in these challenged mice, while mast cell activation, though also dispensable, was an important contributor to the overall anaphylactic response. In our model, proteins must be displayed on the surface of BMDCs to generate a robust antibody response and this process simultaneously required MHC class II presentation. Furthermore, germinal centers were necessary to generate this humoral response: mice lacking T follicular helper cells were not able to generate robust, presumably high-affinity, IgG and IgE responses to the proteins displayed by the transferred BMDCs. Intriguingly, while murine BMDCs could display proteins from both bovine serum and human serum, there was selectivity in the specific proteins they displayed. This selectivity resulted in differential humoral responses in recipient mice. Specifically, transferred murine BMDCs displayed and generated a humoral response to human serum albumin; in contrast, these BMDCs only minimally displayed bovine serum albumin found within fetal bovine serum and could not generate a robust humoral response against it. Previous work has demonstrated that in addition to processing and presenting peptides, DCs may be involved in presenting proteins to B cells. We show here that specific protein display (as distinguished from peptide antigen presentation) may be a function of DCs that contributes in some contexts to humoral immunity.