Role of the BCR complex in B cell development, activation, and leukemic transformation.
A primary focus of signal transduction in B cells, from the pre-B cell to the mature B cell, is the B cell receptor complex. Here we describe work demonstrating the importance of signaling via the pre-B cell receptor complex (pre-BCR) to the pre-B cell transition, the central checkpoint in B-cell development. We have shown tht pre-BCR complex components Igalpha and Igbeta are critical to allowing the pre-B cell to move through this transition, but may not be required for allelic exclusion. Pre-BCR expression also directly affects the response of leukemic cells to steroid treatment, suggesting that signals initiated by the pre-BCR complex may present therapeutic targets in acute leukemia. Additionally, interleukin-7 may also modulate the response of leukemic cells arising from early B-cell stages to treatment. This observation has lead directly to proposals to test drugs which may antagonize early B-cell growth signals, such as rapamycin, in acute lymphoid leukemia.
Rheingold
Susan R
SR
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Brown
Valerie I
VI
Fang
Junjie
J
Kim
Jenny M
JM
Grupp
Stephan A
SA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D006801:Humans; D007938:Leukemia / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell