Censoring of autoreactive B cell development by the pre-B cell receptor

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.