The reduced expression of surrogate light chains in B cell precursors fromsenescent 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, lambda 5 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 mon ths old BALB/c mice after stimulation with IL-7. Both lambda 5 and VpreB ex pression were decreased at the mRNA level as indicated by semi-quantitative RT-PCR; this suggests that the reduced surrogate light chains seen in sene scent B cell precursors result from dysfunctional transcriptional regulatio n. The transcription of surrogate light chains is regulated, in part, by E2 A (E47) gene products. Levels of E2A proteins, including E47, were decrease d in senescent B cell precursors by up to 90%. Reduced E2A (E47) expression and subsequent reduced transcription of the surrogate light chain componen ts lambda 5 and VpreB may, in part, explain the diminished production of B lineage cells observed in senescence. (C) 2000 Elsevier Science Ireland Ltd . All rights reserved.