Surrogate-light-chain silencing is not critical for the limitation of pre-B cell expansion but is for the termination of constitutive signaling.
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.
van Loo
Pieter Fokko
PF
Department of Immunology, Erasmus Medical Center Rotterdam, P.O. Box 2040, NL-3000 CA Rotterdam, The Netherlands.
Dingjan
Gemma M
GM
Maas
Alex
A
Hendriks
Rudi W
RW
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000276:immunology; D020868:Gene Silencing; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000235:genetics* / Q000276:immunology*; D054444:Immunoglobulin Light Chains, Surrogate; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology
D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D008562:Membrane Glycoproteins