Article

Immunologic Research

, Volume 27, Issue 2, pp 309-329

Role of the BCR complex in B cell development, activation, and leukemic transformation

  • Susan R. RheingoldAffiliated withDivision of Oncology, Children's Hospital of PhiladelphiaSchool of Medicine, University of Pennsylvania
  • , Valerie I. BrownAffiliated withDivision of Oncology, Children's Hospital of PhiladelphiaSchool of Medicine, University of Pennsylvania
  • , Junjie FangAffiliated withDivision of Oncology, Children's Hospital of Philadelphia
  • , Jenny M. KimAffiliated withDivision of Hematology/Oncology, Children's Hospital
  • , Stephan A. GruppAffiliated withDivision of Oncology, Children's Hospital of PhiladelphiaSchool of Medicine, University of Pennsylvania Email author 

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Abstract

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 Igα and Igβ are critical to allowing the pre-B cell to move through thistransition, 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 targetsin 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.

Key Words

B cell receptor complex Pre-B cell receptor Cytoplasmic μ B-cell development