Human IgM anti-IgM cytotoxin for B lymphocytes

Area of Science:

• Immunology
• Cell Biology

Background:

• B lymphocytes can be killed by cold-reactive antibodies in human serum at 5°C.
• The specific targets of these cold cytotoxins on B lymphocytes have not been fully elucidated.

Purpose of the Study:

• To identify the molecular targets of cold-reactive cytotoxins found in human serum that affect B lymphocytes.
• To characterize the binding properties and specificity of these cold-reactive antibodies.

Main Methods:

• Immunoaffinity chromatography using IgG- and IgM-coupled Sepharose beads to isolate cytotoxic antibodies from serum.
• Acid elution to recover bound antibodies from the affinity columns.
• Radioiodination (125I) of eluted antibodies for binding assays.
• Inhibition assays using purified immunoglobulins (IgG, IgM) to assess binding specificity.

Main Results:

• Cold cytotoxic activity in serum was predominantly removed by IgM-coupled Sepharose, with partial removal by IgG-coupled Sepharose.
• Eluted antibodies showed avid binding to both IgM- and IgG-coupled beads, with a stronger preference for IgM.
• The eluted antibodies recognized common determinants on both IgM and IgG.
• IgM significantly inhibited the cytotoxicity of the eluted antibodies.

Conclusions:

• Cold-reactive cytotoxins targeting B lymphocytes are primarily directed against surface immunoglobulins, particularly IgM.
• The findings suggest a potential regulatory role for IgM anti-immunoglobulin antibodies in immune responses via B-lymphocyte binding.