TRAPnSeq allows high-throughput profiling of antigen-specific antibody-secreting cells

Area of Science:

• Immunology
• Molecular Biology
• Biotechnology

Background:

• B cells differentiate into antibody-secreting cells (ASCs) after antigen activation.
• Antigen-specific B cells expressing B cell receptors (BCRs) are easily profiled.
• Antigen-specific ASCs lack surface BCRs, hindering their profiling and characterization.

Purpose of the Study:

• To develop a method for profiling antigen-specific ASCs.
• To enable high-throughput screening of single ASCs against large antigen panels.
• To accelerate therapeutic antibody discovery from ASCs.

Main Methods:

• TRAPnSeq (antigen specificity mapping through immunoglobulin secretion TRAP and Sequencing) captures secreted antibodies on ASC surfaces.
• Combines flow cytometry, microfluidics, and DNA-barcoding technologies.
• Enables single-cell V(D)J, RNA, and antigen barcode sequencing.

Main Results:

• Successfully profiled antigen-specific IgG and IgE ASCs from both mice and humans.
• Demonstrated the capacity of TRAPnSeq for high-throughput screening.
• Highlighted the utility of the method for therapeutic antibody discovery.

Conclusions:

• TRAPnSeq provides a novel approach for characterizing antigen-specific ASCs.
• The method overcomes limitations in profiling ASCs lacking surface BCRs.
• TRAPnSeq facilitates efficient discovery of therapeutic antibodies.