Figure 1. Stages of B-cell development.

B-cell development occurs in both the bone marrow and peripheral lymphoid tissues such as the spleen. In the bone marrow, development progresses through the pro-B-cell, pre-B-cell and immature-B-cell stages. During this differentiation, rearrangements at the immunoglobulin locus result in the generation and surface expression of the pre-B-cell receptor (pre-BCR, which is comprised of an Igµ heavy chain and surrogate light chains (VpreB or V_λ5)) and finally a mature BCR (comprised of rearranged heavy- and light-chain genes) that is capable of binding antigen. At this immature stage of development, B cells undergo a selection process to prevent any further development of self-reactive cells. Both receptor editing and clonal deletion have a role at this stage. Cells successfully completing this checkpoint leave the bone marrow as transitional B cells, eventually maturing into mature follicular B cells (or marginal-zone B cells). Following an immune response, antigen-specific B cells develop into either plasma (antibody-secreting) cells or memory B cells. Transitional 3 (T3) B cells, once thought to be part of the linear development from immature to mature B cells, are now thought to represent primarily self-reactive anergic B cells (also known as An1 B cells).