Association of the pre-B cell receptor (BCR) expression level with the quality of pre-BII cell differentiation reveals hierarchical pre-BCR function

The expression of a pre-B cell receptor (pre-BCR) is required for allelic exclusion and pre-BII cell differentiation. VH12 μH chains are unusual in that they form pre-BCRs and mediate allelic exclusion, but most cannot drive pre-BII cell differentiation. To explain this paradox, we examined pre-BCR functions and pre-BII cell differentiation in mice expressing μH chain transgenes encoding a B cell-permissible VH12 μH chain (designated 10/G4(6-1)), and a non-permissible VH12 μH chain (designated 8/G0). Compared with 10/G4 pre-BCRs, 8/G0 pre-BCRs are expressed at low levels on the cell surface. 8/G0 pre-BCRs mediate allelic exclusion, but 8/G0 pre-BII cells are defective in proliferation and expression of survival factors Bcl-2, Bcl-XL and hemokinin 1 (HK1). Increasing 8/G0 μH chain production restores HK1 transcription and improves proliferation of pre-BII cells as well as later stage B cell development. These data reveal a hierarchy of pre-BCR function that determines the development and plasticity of early B cells.