B Cell - Development of B Cells

Development of B Cells

Immature B cells are produced in the bone marrow of most mammals. Rabbits are an exception; their B cells develop in the appendix-sacculus rotundus. After reaching the IgM+ immature stage in the bone marrow, these immature B cells migrate to secondary lymphoid tissues (such as the spleen, lymph nodes, Peyer's patches, etc.) where they are called transitional B cells, and some of these cells differentiate into mature B lymphocytes.

B cell development occurs through several stages, each stage representing a change in the genome content at the antibody loci. An antibody is composed of two identical light (L) and two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable) region and the 'C' (Constant) region. In the heavy-chain 'V' region there are three segments; V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell. Similar rearrangements occur for light-chain 'V' region except there are only two segments involved; V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development.

When the B cell fails in any step of the maturation process, it will die by a mechanism called apoptosis, here called clonal deletion. B cells are continuously produced in the bone marrow. When the B cell receptor, on the surface of the cell matches the detected antigens present in the body, the B cell proliferates and secretes a free form of those receptors (antibodies) with identical binding sites as the ones on the original cell surface. After activation, the cell proliferates and B memory cells would form to recognise the same antigen. This information would then be used as a part of the adaptive immune system for a more efficient and more powerful immune response for future encounters with that antigen.

B cell membrane receptors evolve and change throughout the B cell life span. The proteins TACI, BCMA and BAFF-R (B cell activating factor receptor) are present on both immature B cells and mature B cells. Belimumab is a monoclonal inhibitor of the soluble form of B cell activating factor (BAFF), while blisibimod is an inhibitor of both membrane and soluble forms of BAFF. CD20 is expressed on all stages of B cell development except the first and last; it is present from pre-B cells through memory cells, but not on either pre-pro-B cells or plasma cells.