Signal transduction via the B-cell antigen receptor: the role of protein tyrosine kinases and protein tyrosine phosphatases.

Abstract

The B-cell antigen receptor (BCR) complex performs an essential function during B-cell development and differentiation. In pro-B and pre-B cells, expression of the membrane immunoglobulin heavy chain of the BCR in conjunction with pseudo- light-chain gene products is essential for establishing allelic exclusion and for promotion of gene recombination at the light-chain loci. Subsequent expression of a mature BCR complex on the surface of immature B cells is important for tolerance induction and selection into the peripheral B-cell pool. During the process of tolerance induction, binding of self-antigen to the BCR on B cells can lead to anergization, clonal elimination or receptor editing, depending on the qualitative/ quantitative nature of the signal delivered, and the developmental state of the B cell (Goodnow 1996; Hertz and Nemazee 1998; LeBien 1998). Once B cells have been selected and migrate to the periphery, the BCR complex mediates antigen-dependent activation and selection into the memory B-cell pool (CAMBIER et al. 1994; Goodnow and Cyster 1997; Reth and Wienands 1997; MacLennan 1998). It has also been shown recently that expression of the BCR is critical because it provides a persistence signal that is required for maintenance of the primary B-cell repertoire (LAM et al. 1997). The persistence signal does not promote entry into the cell cycle; thus, it is likely that the nature and/or strength of the persistence signal delivered via the BCR is distinct from that of an antigen-driven activation signal which causes the B cell to enter the cell cycle.