The cellular mechanism by which complementary Id + and anti‐Id antibodies communicate: T cells integrated into idiotypic regulation

The V region antigenic determinants (idiotopes (Ids)) of antibodies (Abs) have been suggested to be involved in regulating the immune system. Certain diseases such as diabetes mellitus have recently been associated with a disequilibrium between Id + and anti‐Id Abs. However, it is unknown how Abs carrying complementary idiotypes (that is, Id + and anti‐Id Abs) regulate each other at the level of B and T cells. In this study, we show that B lymphoma cells genetically equipped with anti‐Id BCR V regions receive a signal when exposed to Id + Ig. Moreover, they become × 10 4 more efficient at presenting exogenous Id + Ab to CD4 + T cells in vitro . Activated Id‐specific T cells in turn regulated the Id‐specific B lymphoma cells. Similar results were obtained in vivo in a surrogate model in which an Id‐peptide was incorporated genetically into the C‐region of a recombinant Ab that targeted IgD on B cells. The findings suggest that conventional T–B collaboration can explain communication between complementary Id + and anti‐Id Ab at the cellular level. A model is suggested that integrates present and previous data on B‐cell regulation by Id‐specific T cells.