16 - Transgenic Mouse Model for Peripheral B Cell Tolerance

Abstract

During maturation, B cells migrate from the bone marrow to the spleen and to the other peripheral lymphoid tissues. There, individual B lymphocytes recognize foreign antigens specifically, expand, and differentiate into antibody-producing cells. B cells, like T cells, pass a developmental stage at which they are susceptible to tolerance-inducing signals. This susceptibility should be linked to their failure to express cell surface molecules that function during signal transduction as recipients for activating signals, or intensify the interactions with activating T helper cells. B cell activation involves cooperation with T cells via specific receptor-ligand interactions. For T cells, the interaction of their CD28 receptor molecules with the B7 ligand expressed on the surface of B cells serves as the second, co-stimulatory signal during T cell activation that leads to an increase in the production of cytokines that would activate the B cells. For B cells activated by T cells, a co-stimulatory signal comes from the interaction between the CD40 receptor molecules expressed by B lymphocytes and the CD40 ligand present on the surface of T cells. The blockade of this interaction results in the inhibition of B cell responses. The developmental arrest of those immature cells prevents the expression of adhesion molecules and surface receptors required for full activation during the next stages of B cell maturation. This mechanism might be an important controlling event that enhances the developmental arrest of self-reactive lymphocytes.