The reduced expression of surrogate light chains in B cell precursors from senescent BALB/c mice is associated with decreased E2A proteins

Abstract

Senescent mice exhibit decreased numbers of pre-B cells in the bone marrow. Herein, we show that the molecules, λ5 and VpreB, which comprise the surrogate light chain component of the pre-B cell receptor, are reduced in pro-B/early pre-B cells derived in vitro from the bone marrow of 18–27 months old BALB/c mice after stimulation with IL-7. Both λ5 and VpreB expression were decreased at the mRNA level as indicated by semi-quantitative RT-PCR; this suggests that the reduced surrogate light chains seen in senescent B cell precursors result from dysfunctional transcriptional regulation. The transcription of surrogate light chains is regulated, in part, by E2A ( E47) gene products. Levels of E2A proteins, including E47, were decreased in senescent B cell precursors by up to 90%. Reduced E2A ( E47) expression and subsequent reduced transcription of the surrogate light chain components λ5 and VpreB may, in part, explain the diminished production of B lineage cells observed in senescence.