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Lymphocyte Stimulation with Fc Fragments

I. Class, Subclass, and Domain of Active Fragments¹

From the Department of Immunopathology, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, California 92037

Abstract

The effect of Fab and Fc fragments of immunoglobulins (Ig) of different species and different classes on DNA synthesis of mouse spleen cell cultures was analyzed by measuring ³H-thymidine incorporation. The data show that Fc fragments from mouse IgG induce strong stimulation of DNA synthesis in mouse spleen cells. In contrast, Fc fragments from turkey IgG are not stimulatory. The Fc fragments of all four human IgG subclasses, IgM, IgA1, and IgD, but not IgE, were stimulatory. In contrast, intact Ig and Fab fragments of the same classes had no effect.

Reduction and alkylation of the IgG Fc fragment did not diminish its activity. The pepsin fragment of IgG, pFc', which represents largely the C3 domain, as well as a fragment obtained by trypsin cleavage of Fc also representing the C3 domain, were both able to induce DNA synthesis. However, the activity of these subfragments was only between 10 and 25% of the activity of intact Fc, suggesting that sites in addition to the C3 domain are required for optimal cell activation.

We postulate that enzymatic cleavage of Ig produces a mitogenically active Fc fragment with reactive sites similar to those of the Fc portion of Ig in antigen-antibody complexes or aggregated Ig. DNA synthesis induced by Fc fragments may represent a model of polyclonal lymphocyte activation through the Fc receptor.

Footnotes

¹ This is publication No. 1582 from the Department of Immunopathology, Scripps Clinic and Research Foundation, La Jolla, California. This work was supported in part by American Cancer Society Grant IM42G, and Biomedical Research Support Program Grant (RRO-5514).

² Recipient of National Institutes of Health Fellowship AI-05345 from the National Institute of Allergy and Infectious Diseases. Current address: Centre De Transfusion, Hospital Cantonal, Geneva 4, Switzerland.

³ Recipient of National Institutes of Health Grant AI-10734.

⁴ Recipient of United States Public Health Service Research Career Award 5-K6-GM-6936.