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Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines
Gregory Lee Szeto1, Debra Van Egeren2, Hermoon Worku3
11] Department of Materials Science &Engineering, MIT [2] Department of Biological Engineering, MIT [3] David. H. Koch Institute for Integrative Cancer Research, MIT [4] The Ragon Institute of Harvard, MIT, and MGH.
Scientific Reports
|May 23, 2015
Summary
Mechano-poration enables B-cells to efficiently take up antigens. This technique allows B-cells to prime antigen-specific CD8(+) T-cells in vitro and in vivo, overcoming a key limitation for their use as antigen-presenting cells.
Area of Science:
- Immunology
- Cell Biology
- Biotechnology
Background:
- B-cells are potential antigen-presenting cells (APCs) for T-cell priming.
- Their limited antigen uptake capacity hinders their use compared to dendritic cells.
Purpose of the Study:
- To investigate mechano-poration for enhancing B-cell antigen loading.
- To assess the capacity of mechano-porated B-cells to prime antigen-specific T-cells.
Main Methods:
- Utilized a microfluidic device for high-throughput 'cell squeezing'.
- Mechano-poration induced transient pores for intracellular protein delivery into B-cells.
- Evaluated antigen presentation to CD8(+) and CD4(+) T-cells in vitro and in vivo.
Main Results:
- Mechano-poration enabled efficient antigen delivery into both resting and activated B-cells.
- B-cells presented antigens exclusively to CD8(+) T-cells.
- Primed CD8(+) T-cells exhibited effector functions (granzyme B, interferon-γ).
- Antigen-loaded B-cells successfully primed CD8(+) T-cells in vivo.
Conclusions:
- Mechano-poration is a viable technology for loading antigens into B-cells.
- This method facilitates the priming and expansion of antigen-specific CD8(+) T-cells.
- It decouples antigen uptake from B-cell activation, enhancing their APC function.
