A Possible Role for Idiotype/Anti-idiotype B-T Cell Interactions in Maintaining Immune Memory

Abstract

Variable regions of both B-cell receptors (BCRs) and T-cell receptors (TCRs) are completely formed in the postnatal period, and, consequently, no innate immune tolerance against these structures exists in adulthood. Indeed, antibodies (Abs) specific to TCRs have been found in both animals and humans. These facts clearly indicate the existence of B cells able to directly interact with T cells through binding of BCRs to TCRs without implicating major histocompatibility complex molecules. A novel paradigm is proposed in that the immune memory is based on idiotype/anti-idiotype interactions occurring between BCRs and TCRs following clearance of the antigen that elicited immune responses. It is envisaged that direct contact between memory T and B cells could provide co-stimulatory signals needed to sustain viability, growth, and differentiation of the interacting immune cells. In contrast, plasma cells originating from memory B-cells could produce anti-TCR Abs that inhibit direct BCR-to-TCR interactions, thereby downregulating the B- to T-cell contact-based immune memory via a negative feedback mechanism.

Keywords: B-cell receptor; T-cell receptor; idiotype/anti-idiotype interaction; immune memory; memory B-cell; memory T cell.

Figure 1

A schematic representation of a T–B cell cluster responsible for the immune memory. Direct idiotype (Id)–anti-idiotype (anti-Id) interactions between T- and B-cells, as well as between B- and B-cells, favor membrane and cytokine co-stimulations of both Id+- and anti-Id+ immune cells, thereby maintaining the viability of each other in the absence of antigenic stimulation.

Figure 2

A role for IgG antibodies (Abs) in downregulating immune memory. Direct BCR-to-TCR interactions lead to growth and differentiation of memory B and T cells. Subsequently, plasma cells originated from memory B cells produce IgG Abs, which shield TCRs, thereby inhibiting not only growth and differentiation activity of memory B and T cells but also the functionality of effector T cells, including helper T cells.