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

Senescent mice exhibit decreased numbers of pre-B cells in the bone marrow. Herein, we show that the molecules, lambda5 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 lambda5 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 lambda5 and VpreB may, in part, explain the diminished production of B lineage cells observed in senescence.