Mechanisms of central tolerance for B cells

Abstract

Immune tolerance hinders the potentially destructive responses of lymphocytes to host tissues. Tolerance is regulated at the stage of immature B cell development (central tolerance) by clonal deletion, involving apoptosis, and by receptor editing, which reprogrammes the specificity of B cells through secondary recombination of antibody genes. Recent mechanistic studies have begun to elucidate how these divergent mechanisms are controlled. Single-cell antibody cloning has revealed defects of B cell central tolerance in human autoimmune diseases and in several human immunodeficiency diseases caused by single gene mutations, which indicates the relevance of B cell tolerance to disease and suggests possible genetic pathways that regulate tolerance.