B-cell Development

Overview
  • B-cells develop from Hematopoietic Stem Cells and most of their maturation occurs in the bone marrow although certain final stages occur in the spleen. A review of Antibody structure may be required to fully understand the content of this page (See: Antibody).
Commitment to B-cell Lineage
  • As mentioned, B-cells develop from Hematopoietic Stem Cells in the bone marrow which can give rise to all blood cells. Commitment to the B-cell lineage first occurs through a lymphocyte progenitor stage which can differentiate into any type of lymphocyte including B-cells, T-cells, or Natural Killer Cells. The precise pathways which give rise to the different types of blood cells is discussed in greater detail in hematopoiesis.
Bone Marrow Stages
  • Antibody Synthesis
    • Once committed to the B-cell lineage, cells begin to mutate the genetic locus which encodes the antibody gene in such a way as to generate an Antibody with a completely unique sequence of its variable region (See: Antibody). This mutation process is known as VDJ Recombination and is one of the few physiological processes in which host DNA is intentionality mutated. The end result of these genetic rearrangements is a B-cell which synthesizes an antibody that can bind a completely unique antigen. During the bone marrow stages, B-cells solely the produce the IgM isotype of antibody as a membrane protein. This membrane-bound version of IgM is called the "B-cell Receptor" and binding of antigen can cause activation of signal-transduction pathways within the B-cell.
  • Selection
    • Following rearrangement of the antibody locus, a selection process ensues which guarantees that only those B-cells survive whose antibody cannot bind self-antigen. This is accomplished by instructing any B-cells with self-binding antibodies to undergo apoptosis. Defects in this selection process may be the root cause of some Autoimmune Diseases. Once B-cells have synthesized antibody and undergone selection they exit the bone marrow and travel to the spleen.
Splenic Stages
  • B-cells undergo several "Transitional Stages" within the spleen in which there is yet further selection against those B-cells whose antibody can bind self-antigen. Following this second round of negative selection, B-cells are considered to be naive "Mature B-cells" and travel through the periphery as described below.
Peripheral Stages
  • Mature B-cells are ready for participation in Humoral Immunity. However, these cells require certain activating stimuli prior to differentiation into antibody-secreting effector cells known as Plasma Cells. These activating stimuli require encounter with antigen and certain cytokines derived from Th2 Cells as described further in Humoral Immunity. During these processes, B-cells act as Antigen Presenting Cells (APCs) and in this limited sense, B-cells are considered APCs.