Maintenance of surrogate light chain expression induces developmental delay in early B cell compartment.
The production of a mature B cell requires passage through a number of developmental checkpoints. The pre-BCR plays a critical role in passage through the pro-B cell/pre-B cell checkpoint, and thus plays a central role in regulating the differentiation of a B cell. Due to the significance of this receptor, it is imperative that pre-BCR expression and function are precisely regulated. In this study, we have investigated a system in which the regulation of the pre-BCR is altered. We have found that continued expression of components of the pre-BCR (lambda5) resulted in a delay in the kinetics of B cell maturation. Pro-B cells from normal mouse bone marrow retrovirally infected with lambda5 exhibited a delay in differentiation. As compared with wild-type cells at the same time point, there is a reduction in the presence of cell surface markers that indicate developmental progression, and there is a 6- to 16-fold decrease in the production of Ig-positive cells in B cell maturation assays. The capacity to alter B cell progression by modifying and extending pre-BCR expression argues that the receptor and its associated signals play a unique role in directing developmental outcomes.
Martin
Denise A
DA
Department of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
Lu
Liwei
L
Cascalho
Marilia
M
Wu
Gillian E
GE
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D054444:Immunoglobulin Light Chains, Surrogate / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054420:Pre-B Cell Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
D006131:Growth Inhibitors; D054444:Immunoglobulin Light Chains, Surrogate; D054420:Pre-B Cell Receptors