The pre-B cell receptor in B cell development: recent advances, persistent questions and conserved mechanisms.
B cell development is a process tightly regulated by the orchestrated signaling of cytokine receptors, the pre-B cell receptor (BCR) and the B cell receptor (BCR). It commences with common lymphoid progenitors (CLP) up-regulating the expression of B cell-related genes and committing to the B cell lineage. Cytokine signaling (IL-7, stem cell factor, FLT3-L) is essential at this stage of development as it suppresses cell death, sustains proliferation and facilitates heavy chain rearrangements. As a result of heavy chain recombination, the pre-BCR is expressed, which then becomes the primary determiner of survival, cell cycle entry and allelic exclusion. In this review, we discuss the mechanisms of B cell lineage commitment and describe the signaling pathways that are initiated by the pre-BCR. Finally, we compare pre-BCR and pre-TCR structure, signal transduction and function, drawing parallels between early pre-B and pre-T cell development.
Clark
M R
MR
Section of Rheumatology, University of Chicago, IL 60637, USA. mclark@medicine.bsd.uchicago.edu
Cooper
A B
AB
Wang
L D
LD
Aifantis
I
I
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D005786:Gene Expression Regulation; D006801:Humans; D038041:Lymphopoiesis; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction
D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell