Human DC-SIGN and CD23 do not interact with human IgG

Area of Science:

• Immunology
• Glycobiology
• Pharmacology

Background:

• Intravenous immunoglobulin (IVIg) therapies are used for various inflammatory and autoimmune conditions, but their precise mechanisms remain unclear.
• Sialylated IgG, a fraction within IVIg, shows enhanced therapeutic activity in mouse models.
• Fc-sialylation of IgG may alter its binding properties, potentially mediating immunomodulatory effects through interactions with C-type lectins like DC-SIGN and CD23.

Purpose of the Study:

• To investigate whether human CD23 and DC-SIGN directly bind to human IgG, irrespective of its glycosylation status.
• To determine if Fc- or Fab-glycosylation of IgG influences its interaction with CD23 and DC-SIGN.
• To clarify the role of these C-type lectins in the immunomodulatory mechanisms of IVIg.

Main Methods:

• Utilized flow cytometry (FACS) to assess cellular binding.
• Employed a novel cellular Surface Plasmon Resonance imaging (cSPRi) approach to monitor low-affinity, high-avidity interactions.
• Tested binding of sialylated and non-sialylated human IgG (with variations in glycosylation) to cells expressing human CD23 and DC-SIGN.

Main Results:

• Cells expressing native CD23 and DC-SIGN bound their natural ligands (IgE and ICAM-3, respectively).
• No binding of human IgG to CD23 or DC-SIGN was observed, regardless of Fc- or Fab-glycan sialylation, fucosylation, or bisection.
• The study found no evidence supporting CD23 or DC-SIGN as direct receptors for human IgG.

Conclusions:

• Human CD23 and DC-SIGN do not appear to be direct receptors for human IgG, challenging proposed mechanisms of IVIg therapy.
• The findings do not exclude indirect roles for IgG glycosylation or C-type lectins in modulating IVIg efficacy.
• Further research is needed to fully elucidate the complex mechanisms underlying IVIg's anti-inflammatory effects.