AFCs are short-lived plasmablasts that emerge early in immune responses, producing low-affinity antibodies to neutralize pathogens. Key characteristics include:
Rapid proliferation and decline: AFCs peak within 7 days post-immunization but undergo apoptosis by day 14, limiting their persistence in secondary lymphoid organs .
Surface markers: AFCs express low B220 (CD45R), high syndecan-1 (CD138), and retain surface IgG1, distinguishing them from germinal center B cells .
Role in mucosal immunity: IgA-secreting AFCs dominate mucosal surfaces (e.g., intestines, lungs), aggregating antigens for expulsion via secretions .
Glycosylation: N-linked glycans at Asn297 (IgG) modulate FcγR binding and half-life. Aglycosylated antibodies (e.g., eptinezumab) lack effector functions but retain target neutralization .
Fc engineering: Mutations (e.g., GAALIE variant) enhance FcγRIIIa binding, improving antiviral activity in SARS-CoV-2 therapies .
Although AFC1 is not explicitly cited, Fc-optimized antibodies demonstrate therapeutic relevance:
Antibody | Target | Modification | Effect | Indication |
---|---|---|---|---|
Margetuximab | HER2 | F243L/R292P/Y300L | ↑ADCC, ↓FcγRIIB binding | Metastatic breast cancer |
Envafolimab | PD-L1 | C220S/D265A/P331S | Reduced ADCC/ADCP | Solid tumors |
Levilimab | IL-6R | E233P/L234V/L235A | ↓Effector function, ↑half-life | COVID-19 inflammation |
Antibody-drug conjugates (ADCs): MUC1-targeted ADCs (e.g., M1231) show enhanced tumor internalization in non-small cell lung cancer models .