Curriculum

B-cell development occurs through several discrete stages, at many anatomical locations (reviewed in Ref. 141). In adult mice, B-cell development starts in the bone marrow, whererecombination-activating gene (Rag)-mediated rearrangement of the locus results in the expression of the heavy chain, which associates with the surrogate light chain (SLC) and with Ig and Ig (which transmit signalsinside the cell) to form the pre-B-cell receptor (pre-BCR). Signalling through the pre-BCR promotes a proliferative burst, followed by progression stage to the pre-B-cell stage, where Rag-mediatedrecombination yields the and light chains. This transition is partially dependent on p85 and p110 , as well as the downstream effectors BTK (Bruton agammaglobulinaemia tyrosine kinase) and TEC. Therearranged or light chain replaces the SLC to form the BCR. The BCR signals further development of the immature B cells, which migrate to the spleen (and possibly other locations). There are atleast three distinguishable subsets of mature B cells: conventional follicular B2 cells, marginal-zone (MZ) B cells and B1 cells. MZ B-cell and B1-cell development depend on CD19 and p110 . Whetherthese subsets follow a common progressive developmental pathway or parallel developmental pathways is not entirely clear, but the strength and quality of BCR signals are thought to influence the lineagedecision. After exposure to antigen, B cells undergo terminal differentiation to antibody-secreting plasma cells. PI3K signalling seems to be involved at each of these stages, and is antagonized byphosphatase and tensin homologue (PTEN; shown in a yellow box), as described in the text. BCAP, B-cell PI3K adaptor protein; PI3K, phosphoinositide 3-kinase; TD, thymus dependent; TI-2, thymusindependent type 2.



The molecular details of the recruitment and activation of phosphoinositide 3-kinases (PI3Ks) by the B-cell receptor (BCR) is not completely understood, but is at least in part...