Censoring of Autoreactive B Cell Development by the Pre-B Cell Receptor

ArticleinScience 321(5889):696-9 · July 2008with11 Reads
Impact Factor: 33.61 · DOI: 10.1126/science.1157533 · Source: PubMed

    Abstract

    Antibody diversity occurs randomly as B cells recombine their immunoglobulin (Ig) heavy- and light-chain genes during development.
    This process inevitably generates reactivity against self structures, and several mechanisms prevent the development of autoreactive
    B cells. We report here a role for the pre-B cell receptor, composed of Ig heavy and surrogate light chains, in the negative
    selection of cells expressing Ig heavy chains with the potential to generate autoantibodies. Surrogate light-chain–deficient
    (SLC–/–) mice harbored elevated levels of antinuclear antibodies (ANAs) in their serum and showed evidence of escape of pre-B cells
    expressing prototypic autoantibody heavy chains from negative selection, leading to mature autoantibody secreting CD21–CD23– B cells in the periphery. Thus, the pre-B cell receptor appears to censor the development of certain autoantibody-secreting
    cells and may represent an important factor in multifactorial autoimmune diseases.