A functional spleen contributes to afucosylated IgG in humans

Area of Science:

• Immunology
• Glycobiology
• Hematology

Background:

• The spleen is a key lymphoid organ involved in immune responses, particularly to viral infections and alloantigens.
• N-linked glycans on the fragment crystallizable (Fc) region of immunoglobulin G (IgG) influence immune effector functions.
• Afucosylated IgG, with reduced fucose on Fc glycans, is implicated in immune thrombocytopenia (ITP) pathogenesis.

Purpose of the Study:

• To investigate the spleen's role in modulating humoral responses and IgG-Fc glycosylation.
• To test the hypothesis that the spleen is a preferential site for generating afucosylated IgG responses.

Main Methods:

• Analyzed IgG subclass-specific Fc glycosylation using liquid chromatography-mass spectrometry (LC-MS).
• Studied a cohort of individuals who underwent splenectomy (due to trauma, ITP, or spherocytosis) and healthy controls.

Main Results:

• Splenectomy consistently increased IgG-Fc fucosylation, with no changes in galactosylation or sialylation.
• An increase in IgG1- and IgG2/3-Fc fucosylation post-splenectomy was observed for the first time.
• ITP patients showed decreased total IgG-Fc fucosylation compared to healthy controls.

Conclusions:

• The spleen plays a significant role in the induction or maintenance of afucosylated IgG responses by B cells.
• Immune responses within the spleen may be particularly prone to generating afucosylated IgG.
• Findings suggest a novel role for the spleen in IgG glycosylation and its potential involvement in ITP.