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

作者：Wang Hongsheng; Clarke Stephen H^*

来源：Molecular Immunology, 2007, 44(7): 1765-1774.

DOI：10.1016/j.molimm.2006.07.301

• IL-7
• hemokinin 1
• V(H)12
• positive selection

The expression of a pre-B cell receptor (pre-BCR) is required for allelic exclusion and pre-BII cell differentiation. V-H 12 mu H 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 mu H chain transgenes encoding a B cell-permissible V(H)12 mu H chain (designated 10/G4(6-1)), and a non-permissible V(H)12 mu H 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, BCI-X-L and hemokinin 1 (HK1). Increasing 8/G0 mu H chain production restores HKI 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.

• 出版日期2007-3