FIGURE 2 | A pathway for early B-cell differentiation and environmental factor requirement in the bone marrow.

From the following article:

Microenvironmental niches in the bone marrow required for B-cell development

Takashi Nagasawa

Nature Reviews Immunology 6, 107-116 (February 2006)

doi:10.1038/nri1780

Microenvironmental niches in the bone marrow required for B-cell development

Haematopoietic stem cells(HSCs) are highly purified as lineage (Lin)-B220-KIT+SCA1+ fms-related tyrosine kinase 3 (FLT3)-CD34- cells. Lin-B220-KIT+SCA1+FLT3-CD34+ cells are thought to be enriched for non-self-renewing haematopoietic multipotential progenitors (MPPs). Lin-B220-KIT+SCA1+FLT3+ cells lack erythro-megakaryocytic differentiation potential but retain myeloid-cell, B-cell and T-cell potential and are termed lymphoid-primed multipotential progenitors (LMPPs). Lin-KITlowSCA1lowinterleukin-7 receptor (IL-7R)+ cells can give rise to B cells and T cells but not myeloid-lineage cells, and are a common lymphoid progenitor (CLP) population. B-cell precursors, consisting of cells that are negative for cell-surface immunoglobulin (Ig) but positive for the B-cell-lineage marker B220 can be divided into four subsets according to their differential expression of a range of cell-surface markers during development. These four subsets are termed fractions A (pre-pro-B cells), B (pro-B cells), C (pro-B cells) and D (pre-B cells). Immature B cells, which are generated from fraction D cells, exit the bone marrow and reach the spleen, where they mature into peripheral mature B cells and plasma cells. CXC-chemokine ligand 12 (CXCL12) is essential for the generation of pre-pro-B and pro-B cells and for the homing of plasma cells to the bone marrow, but its requirement by LMPPs and CLPs has not been determined. FLT3 ligand (FLT3L) is essential for the generation of CLPs and pre-pro-B cells. IL-7 is essential for the generation of pro-B and pre-B cells but possibly not CLPs or pre-pro-B cells. IL-7 is required for B-cell differentiation potential of CLPs and pre-pro-B cells. Stem-cell factor (SCF) has an essential role in adults from the pro-B-cell stage. Receptor activator of nuclear factor-kappaB ligand (RANKL) is involved in the generation of pre-B cells and immature B cells. ETP, early T-cell-lineage progenitor; NK, natural killer.

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