基础免疫学基础免疫学1 development基础免疫学.pdf

Biochemical Journal (2019) 476 769–778 /10.1042/BC Review Article Signalling circuits that direct early B-cell development Georg Petkau and Martin Turner Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, U.K. Correspondence: Georg Petkau (Georg.Petkau@babraham.ac.uk) In mammals, the B-cell lineage arises from pluripotent progenitors in the bone marrow. During their development, B-cells undergo lineage specification and commitment, followed by expansion and selection. These processes are mediated by regulated changes in gene expression programmes, rearrangements of immunoglobulin (Ig) genes, and well-timed rounds of proliferation and apoptosis. Many of these processes are initiated by environmen- tal factors including cytokines, chemokines, and cell–cell contacts. Developing B-cells process these environmental cues into stage-specific functions via signalling pathways including the PI3K, MAPK, or JAK-STAT pathway. The cytokines FLT3-Ligand and c-Kit-Ligand are important for the early expansion of the B-cell precursors at different developmental stages and conditions. Interleukin 7 is essential for commitment to the B-cell lineage and for orchestrating the Ig recombination machinery. After rearrangement of the immunoglobulin heavy chain, proliferation and apoptosis, and thus selectio