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

Abstract

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 Â10 4 more efficient at presenting exogenous Id + Ab to CD4 + T cells in vitro. Keywords: immune regulation; idiotypic network; immunoglobulins; B cells; T cells; B-to T-cell collaborationThe V regions of immunglobulin (Ig) molecules are extremely diversified. 1 As a consequence, individual Ig molecules carry unique V region antigenic determinants that are called idiotopes (Ids). 2 The network theory 3 suggests that a complex web of idiotypic interactions between Ig may regulate the immune system, although the mechanisms have been poorly defined. The network theory generated numerous supportive publications during the 1970s and 1980s, but the inherent complexity of the theory and relative obscurity of operating mechanisms have sidelined the field. However, during recent years, there seems to be a renewed interest in network theory and its regulatory role in disease. [4][5][6][7] A central tenet of the network theory is that the interaction between Id + and anti-Id Ig has regulatory consequences. The original network theory 3 dealt only with Ig, However, thymectomized 8 and nude 9 mice failed to produce anti-Id antibodies (Abs) on immunization with Id + Ig, showing that Ig molecules are indeed T-cell dependent antigens (Ags). Thus, T cells need yet to be integrated into idiotypic regulation.It has previously been shown that extracellular Id + Ig is endocytosed and processed by Ag-presenting cell, resulting in Id-peptides that are presented on major histocompatibility complex (MHC) class II molecules to Id-specific CD4 + T cells. [10][11][12] Thus, MHC-restricted T cells appear to recognize Ig by the same rules as those that apply to recognition of proteins in general. However, these investigations were carried out with nonspecific Ag-presenting cell and the importance of anti-Id B cells as Ag-presenting cell has yet to be studied. This is the focus of our present investigation. More specifically, we have addressed whether the principle of conventional T-B collaboration 13,14 may explain the link between Id + and anti-Id Abs.Circumstantial evidence supports this idea. Thus, in transfer studies, mice that received M315-primed B cells, M315L chain-primed T cells and M315 myeloma protein, developed an anti-Id Ab response. 15 In addition, B cells whose BCR was ligated by an Ig allotype-specific mAb, efficiently presented an Id-peptide (derived from the allotype-specific mAb) to T cells. 16 Finally, when recombinant Ig (rIg) with Id-peptide genetically integ...

Idiotype-Specific Th Cells Support Oligoclonal Expansion of Anti-dsDNA B Cells in Mice with Lupus

“…It is increasingly clear that Abs are conventional Ags for Th cell and B cell immune responses (55,56). Thus, anti-Id B cells that can bind a particular Ab (e.g., an Id + antidsDNA Ab) internalize this Id + Ab and may elicit help from Idspecific Th cells, the same Th cells that initially could have delivered Id-dependent help to the anti-dsDNA Id + B cell (55,56). In these terms, pathogenic Abs are counter-balanced by Id-driven help of anti-Id B cells.…”

Changes in GAD65Ab-Specific Antiidiotypic Antibody Levels Correlate with Changes in C-Peptide Levels and Progression to Islet Cell Autoimmunity

“…Recently, the uptake of anti-Id by B lymphocytes and presentation of anti-Id peptides on human leukocyte antigen class II molecules, leading to T cell stimulation has been reported (42,43). These studies suggest an idiotypic network consisting of antibodies, anti-Id, T cells, and B lymphocytes.…”

Mechanisms of Immunological Tolerance Disruption

“…Среди других причин дисфунк-ции Treg-клеток рассматривается нарушенная регуляция апоптоза. Показано, что Tregs имеют повышенную чувствительность к индукторам апоптоза у больных СКВ , СД1 [Jailwala et al, 2009].…”