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Publication : Surrogate-light-chain silencing is not critical for the limitation of pre-B cell expansion but is for the termination of constitutive signaling.

First Author  van Loo PF Year  2007
Journal  Immunity Volume  27
Issue  3 Pages  468-80
PubMed ID  17869135 Mgi Jnum  J:125321
Mgi Id  MGI:3758163 Doi  10.1016/j.immuni.2007.07.018
Citation  Fokko van Loo P, et al. (2007) Surrogate-light-chain silencing is not critical for the limitation of pre-B cell expansion but is for the termination of constitutive signaling. Immunity 27(3):468-80
abstractText  The pre-B cell receptor (pre-BCR), composed of immunoglobulin mu heavy chain and the surrogate light chain (SLC) proteins lambda5 and Vpreb, signals for proliferation and maturation of developing pre-B cells. It has been assumed that pre-B cells stop cycling by the pre-BCR-mediated downregulation of SLC transcription. We generated transgenic mice expressing SLC throughout B cell development and, remarkably, found that enforced SLC expression had no effect on pre-B cell proliferation or differentiation. However, in the presence of conventional immunoglobulin light chains, SLC components had the capacity to induce constitutive BCR internalization, secondary immunoglobulin light-chain rearrangement, and a severe developmental arrest of immature B cells, dependent on the adaptor protein Slp65. Residual B cells in the spleen showed increased expression of surface CD5, which is a negative regulator of BCR signaling, and differentiated spontaneously into IgM+ plasma cells. Thus, the silencing of SLC genes is not essential for the limitation of pre-B cell proliferation, but is required for the prevention of constitutive activation of B cells.
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