ABSTRACT
Lymphoid cells are derived from a common lymphoid progenitor, which has the capacity to develop into T, B, or natural killer (NK) cells.1 Subsequently, a B-cell precursor, which differs from the T-, NK-, and dendritic cell precursor,
leads to the development of the first recognizable B-cell type, a pro B cell (Fig. 3.1). At least three transcription factors have been identified as being essential for B-cell commitment. These include E2A
2 and EBF,3 both basic helix-loop-helix proteins, in the absence of which no B-cell progenitors develop. A third factor, Pax 5, is also essential
Stem cell
V(D)J gene rearrangement
Pro-B Pre-B Immature B
Mature B
Plasma cell
Memory B
IgM IgM IgD
Membrane Ig expression
Surface markers
CD34 CD19 CD10 TdT
CD34
CD19 CD10 CD20
clg
CD19 CD20 lgM
CD19 CD20 lgM
CD19 slg lgD
CD38hi
CD138 clg
DH – JH VH – DH – JH VL K or λ
surrogate light chains
IgM Isotype switch to
IgG, lgA or IgE
No membrane
expression – secretes lg
IgM IgD
for B commitment.4 B-cell development takes place in the bone marrow from mid-gestation onwards. The pro B cell, which expresses cell surface CD19 but not cytoplasmic immunoglobulin, undergoes rearrangement of its immunoglobulin heavy chain. This is then associated with the products of variable pre-beta and lambda 5 genes, which encode proteins that associate with each other to form the surrogate light chain.5 Covalently bound and surrogate light chains are only expressed on the surface of B-lineage precursors. The surrogate light chain expression disappears with more mature B-cell development. Its expression early in B-cell ontogeny allows the variable regions of the heavy chain (in conjunction with the surrogate light chain) to be exposed to stromal cells, a requirement for the production of cytokines involved in B-cell development.6 Subsequent rearrangement of the true light chain gene enables the cell (the immature B cell) to formally express surface IgM. The immature B cell thus expresses CD19 as well as cell-surface IgM associated with kappa or lambda light chains, i.e. the B-cell receptor. Immature B lymphocytes are able to leave the bone marrow, circulate in the blood and develop the ability to express surface IgD. A virgin B cell is an IgM, IgD peripheral blood cell, which is in Go phase of the cell cycle. Such cells may be activated, proliferate and give rise to both plasma cells and memory B cells. Such activation requires contact with T cells.
