Induction of anti-H–2 antibodies without alloantigen exposure by in vivo administration of anti-idiotype

Abstract

Anti-idiotypic reagents have been used recently to manipulate both idiotype (ID) expression and antigen-binding antibody activity of immunized animals^1–11. The in vivo administration of anti-idiotypic antibodies followed by antigen exposure has usually resulted in suppression of ID-positive antigen binding molecules^6–8, although, in other circumstances, increased idiotype expression and antigen-binding activity has also been observed^1–5. Extension of these findings to the immune response to transplantation antigens is of obvious practical and theoretical importance. There have been several reports describing the production of anti-idiotypic reagents against alloantisera^9–11, although the generation of anti-ID antibodies in this way has generally been difficult to reproduce¹¹. Therefore, in the study reported here we used xenogeneic anti-idiotypic antisera raised against monoclonal anti-H–2K^k antibodies which offer the advantage of reproducibility of anti-idiotype production¹². These anti-idiotypic reagents were produced by immunizing swine and rabbits with either purified 3-83P¹³ or 11-4.1 (ref. 14), both of which are IgG2a, k anti-H–2K^k antibodies. We found that none of these reagents detected significant levels of idiotype in anti-H–2 antisera produced against H–2K^k antigens by conventional means. However, BALB/c mice treated with these anti-idiotypes consistently produced large amounts of idiotype, and in some animals this induced response included idiotype-positive antibodies which bound to H–2K^k antigens. Thus, treatment with anti-idiotype has been found to induce anti-H–2K^k antibodies in the absence of exposure to the H–2K^k antigen.