Origin of B cells
B-cell/ B Lymphocytes development begins in bone marrow with the asymmetric division of an HSC and continues through a series of progressively more differentiated progenitor stages to the production of Common Lymphoid Progenitors (CLPs), which can give rise to either B cells or T cells.
Progenitor cells that remain in bone marrow become B cells. B cell precursors, during embryogenesis, first proliferate and develop in fetal liver. From there, they migrate to bone marrow, the main site of B-cell maturation in adults. The Pre-B cells have only µ heavy chains in the cytoplasm but do not have surface immunoglobulin and light chains. Pre-B cells are found in the bone marrow, while mature B cells are found in the circulation.
Produced in bone marrow, B cells migrate to spleen and other secondary lymphoid tissues where they mature and differentiate into immunocompetent B cells. According to clonal selection theory, each immunologically competent B cell possesses receptor for either IgM or IgD that can combine with one antigen or closely related antigens. After binding of antigen, B cell is activated to proliferate and form a clone of cells. Selected B cells are transformed to plasma cells that secrete antibodies against specific antigen. Plasma cells synthesize immunoglobulins with same antigenic specificity as those carried by activated B cells.
B cells possess surface IgM, which acts as a receptor for antigen. Some B cells may also carry on their surface IgD as receptor for antigen. There are many other molecules expressed on the surface of B cells, which serve different functions. A few of them are B220, class II MHC molecules, CR1 and CR2, CD40, etc.
Activation of B cells
Exposure to antigen or various polyclonal mitogens activates resting B cells and stimulates their proliferation. Activation of B cells occurs via antigen recognition by B cell receptors (BCR) and a required co-stimulatory, secondary activation signal provided by either helper T cells or antigen itself. This results in stimulation of B cell proliferation and formation of germinal centers where B cells differentiate into plasma cells or memory B cells. Importantly, all B cells derived from a specific progenitor B cell are clones that recognize same antigen epitope.
Activation of B cells first requires recognition of epitope by surface receptor and production of IL-4 and IL-5 by helper T cells. In addition, it also requires other co-stimulatory interactions:
- CD28–B7 interaction (CD28 on T cells with B7 on B cells) essential to produce IL-2.
- CD40L–CD40 interaction (CD40L on T cells, with CD40 on B cells) for class switching from IgM to IgG and switching between other immunoglobulin classes.
Plasma cells are found in spleen and lymph nodes and are responsible for secreting different classes of clonally unique antibodies that are found in blood. Following primary response, a small number of B cells develop into memory B cells, which express high-affinity surface immunoglobulins (mainly IgG), survive for a longer period of time, and enable a rapid secondary response.
In short, B-cells are activated by binding of an antigen to receptors on its cell surface which causes them to divide and proliferate. Some stimulated B-cells become plasma cells, which secrete antibodies. Others become long-lived memory B-cells which can be stimulated later time to differentiate into plasma cells.