Antigen phagocytosis by B cells is required for a potent humoral response.

Ana Martínez‐Riaño,Elena R Bovolenta,María Jesús Martín‐Bermejo,Clara L Oeste,Pilar Mendoza,Martin Turner,Paola Bovolenta,Nuria Martínez‐Martín,Balbino Alarcón

doi:10.15252/embr.201846016

Ana Martínez‐Riaño, Elena R Bovolenta + Show 7 more

Open Access

https://doi.org/10.15252/embr.201846016

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Abstract

Successful vaccines rely on activating a functional humoral response that results from promoting a proper germinal center (GC) reaction. Key in this process is the activation of follicular B cells that need to acquire antigens and to present them to cognate CD4 T cells. Here, we report that follicular B cells can phagocytose large antigen‐coated particles, a process thought to be exclusive of specialized antigen‐presenting cells such as macrophages and dendritic cells. We show that antigen phagocytosis by B cells is BCR‐driven and mechanistically dependent on the GTPase RhoG. Using Rhog −/− mice, we show that phagocytosis of antigen by B cells is important for the development of a strong GC response and the generation of high‐affinity class‐switched antibodies. Importantly, we show that the potentiation effect of alum, a common vaccine adjuvant, requires direct phagocytosis of alum–antigen complexes by B cells. These data suggest a new avenue for vaccination approaches by aiming to deliver 1–3 μm size antigen particles to follicular B cells.

Highlights

The humoral response is essential for the efficacy of most vaccines by generating high-affinity immunoglobulins that are able to neutralize the infection before it has spread in an uncontrollable manner
We wondered whether follicular B cells, to B1 B cells [13,15], could directly phagocytose particulate antigens
We showed that B cells incubated at 37°C and permeabilized with detergent became all positive for anti-goat Ig staining, indicating that anti-goat Ig negative B cells had truly phagocytosed the beads (Fig EV1B)

Summary

Introduction

The humoral response is essential for the efficacy of most vaccines by generating high-affinity immunoglobulins that are able to neutralize the infection before it has spread in an uncontrollable manner. To determine if phagocytosed antigen was presented to T cells, purified WT and RhogÀ/À B cells were incubated with different bead/ B-cell ratios of 1 lm beads coated with anti-IgM plus ovalbumin and subsequently were cultured with purified Cell Trace Violet (CTV)-labeled CD4 T cells from an OT2 transgenic mouse (Fig 1F).

Results

Conclusion