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Immunologic Tolerance in C4 Deficient Guinea Pigs

From the Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20014

Abstract

The precise mechanisms by which immunologic tolerance is induced have not as yet been elucidated. There are a variety of different types of tolerance (1–3) and tolerance in both thymus-derived lymphocytes (T lymphocytes)² and bone marrow-derived lymphocytes (B lymphocytes) has been described (4).

Tolerance induction may involve the destruction of specific immuno-competent cells upon contact with antigen. Support for this concept comes from the finding by some investigators that the number of antigen-binding cells, which appear to be precursors of antibody-secreting cells, are reduced in tolerant animals (5, 6). One possible mechanism for tolerance induction is that antigen, upon reacting with cell surface-bound immunoglobulin receptors, may under certain conditions activate complement at the surface of the cell and thus cause destruction of these cells. Azar et al., following this line of reasoning, have produced a transient complement deficiency in mice with a variety of agents and have reported that in such temporarily complement deficient animals tolerance is more difficult to achieve than in normal animals (7–9).

Footnotes

² Abbreviations used in this paper; T, thymus derived; B, bone marrow derived; DNP, dinitrophenyl; D-CL, copolymer of D-glutamic acid and D-lysine; DNP-D-GL, DNP with D-GL; GPA, guinea pig albumin; PLL, poly-L-lysine homopolymer; BSA, bovine serum albumin; ABC, antigen-binding capacity.

¹ Present address: Department of Pathology and Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.