Figure 1. CXCR4 and B-cell development.

CXCR4 is involved in maintaining the HSC pool throughout contacts with CXCL12-abundant reticular cells in the BM. The level of CXCR4 expression varies during B-cell differentiation. Pro-B cells undergo intensive proliferation in the vicinity of IL-7⁺ CXCL12⁺ stromal cells. An up-regulation of CXCR4 expression characterizes pre-B-cell stage, with disengagement from IL-7–rich niches. Then, the low level of CXCR4 expression in immature B cells induces BM egress to secondary lymphoid organs (see paragraph “Central development: from hematopoietic stem cells to immature B cells”). During the T-dependent response in the germinal center, centroblasts in the dark zone, abundant in CXCL12-expressing stromal cells, strongly express CXCR4, and undergo proliferation and somatic hypermutation. Centrocytes down-regulate CXCR4 to enter the light zone through the CXCL13/CXCR5 axis. Plasma cells emerging from the germinal center re-express CXCR4 and accumulate in the BM, where some of them mature into long-lived plasma cells. Regulation of CXCR4 signaling is also required to limit extrafollicular response and avoid plasmablast accumulation in the BM (see paragraph “From mature B cells to antibodies response”). BCR, B-cell receptor; CAR, CXCL12-abundant reticular cells; CLP, common lymphoid progenitor; HSC, hematopoietic stem cell; SHM, somatic hypermutation. The figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 Unported license.