Natural antibodies to glycans

Area of Science:

• Immunology
• Glycobiology
• Biochemistry

Background:

• Natural antibodies (nAbs), produced by B-1 cells, target a wide array of glycans.
• These nAbs are categorized into conservative, allo-antibodies, and plastic antibodies, with the latter group showing dynamic changes in levels during disease and physiological states.
• The human nAb repertoire against glycans is extensive, with some nAbs comprising up to 0.1% of total immunoglobulins, predominantly of the IgM class.

Purpose of the Study:

• To explore the diversity and specificity of the human natural antibody repertoire directed against glycans.
• To investigate the potential of certain nAbs as diagnostic markers for diseases, particularly focusing on changes in 'plastic' antibodies.
• To understand the functional implications of nAbs, especially anti-core antibodies, in surveillance for aberrant antigens.

Main Methods:

• Utilized modern microarray technology to determine the breadth of the human glycan-directed nAb repertoire.
• Quantified the levels and characterized the specificities of various nAbs, including those targeting specific glycan structures like Le(C), 4'-O-SuLN, and hyaluronic acid.
• Analyzed the affinity of nAbs, typically in the range of 10(-4)-10(-6) M for monovalent glycans.

Main Results:

• Revealed an unexpectedly broad repertoire of human nAbs against glycans, with significant levels of certain antibodies.
• Identified specific nAbs targeting structures such as Galβ1-3GlcNAc (Le(C)), 4-HSO3Galβ1-4GalNAc (4"-O-SuLN), and hyaluronic acid.
• Observed a lack of antibodies against certain glycans (e.g., Le(X), Le(Y), gangliosides) in healthy individuals and noted that many nAbs target the core structures of glycans.

Conclusions:

• Natural antibodies against glycans represent a vast and diverse system with potential clinical applications, particularly as disease biomarkers.
• The presence of nAbs targeting core glycan structures suggests a potential role in immune surveillance against abnormal cell surface antigens, including those found in cancer.
• Further research into the quantitation of anti-glycan nAbs is warranted for diagnostic purposes, especially in oncology.