Signaling through the B cell antigen receptor in developing B cells

Abstract

Signaling events arising from the B cell antigen receptor (BCR) complex are critical for the normal progression of a B cell through its stages of maturation. These stages are characterized by the generation and expression of BCR components. Initially, the heavy chain is formed and expressed along with the surrogate light chain and VpreB. This pre-BCR may initiate events that induce the cell to generate the light chain molecules. Proper expression of these molecules triggers the cell to develop into a mature B cell. If a key signal is absent at any stage of B cell development, maturation ceases, and either the defects are corrected or the cell undergoes apoptosis. A deficiency in the expression of several intracellular proteins required for these signaling events leads to the arrest of B cell development. Advancement to specific stages of maturation relies on a particular intensity of signal through pathways leading to the activation of a set of transcription factors. These pathways include the calcium and MAPK family pathways. Factors such as the concentration and avidity of the antigen, the coligation of co-receptors, and the formation of signaling complexes dictate the intensity of these signals and thereby the fate of the B cell at each stage of development.