Reprogramming human B cells with custom heavy chain antibodies

Area of Science:

• Immunology
• Molecular Biology
• Genetic Engineering

Background:

• The immunoglobulin heavy chain (IgH) locus in B cells controls antibody production.
• Reprogramming B cells offers a novel therapeutic strategy.

Approach:

• Developed a genome editing platform to modify the IgH locus in human B cells.
• Created custom heavy chain antibodies (HCAbs) with antigen-recognition domains linked to Fc domains.
• Engineered HCAbs for differential splicing to express B cell receptor (BCR) or secreted antibody isoforms.

Key Points:

• The HCAb platform is versatile, accommodating various antigen-binding domains and Fc modifications.
• Edited B cells successfully expressed anti-HIV Env HCAbs, functioning as both BCRs and secreted antibodies.
• Demonstrated antigen-specific B cell responses in a tonsil organoid model.

Conclusions:

• Human B cells can be reprogrammed using genome editing to produce customized therapeutic molecules.
• This approach enables the regulated expression of BCRs and antibodies for targeted therapies.
• The strategy holds potential for *in vivo* amplification of therapeutic molecules.