B and T cells development
Affinity maturation
is the process of enhancing the hypervariable region antigen binding affinity that occurs after initial binding of antigen to membrane-bound immunoglobulin on a naive B lymphocyte and subsequent migration of that B-lymphocyte to a lymph node.
Within the germinal center of the L/N, affinity maturation is accomplished by the process of somatic hypermutation where the DNA coding for the immunoglobulin variable region is mutated randomly at a very high rate --> new immunoglobulins with similar, better, or worse affinity for the antigen;
only B cells expressing Ab with enhanced affinity for Ag will be selected for.
B-cell precursors proliferate and mature in the bone marrow. Mature B-cells then leave the bone marrow and migrate to lymphoid organs and peripheral tissues, where they are exposed to antigens. On first exposure to a new antigen, a clone of B-cells becomes activated. Some activated B-cells differentiate into short-lived plasma cells that release antigen-specific IgM through a T-cell independent process. However, most activated B-cells migrate to lymphoid follicles located in the lymph node cortex where they form germinal centers (arrows) that are the site of B- cell proliferation during the immune response. A portion of these activated B-cells form long-lived memory cells that remain dormant in the lymph node until the next encounter with the same antigen, but the majority transform into antibody-secreting plasma cells.
Isotype switching (from IgM to other types of immunoglobulins) also occurs in the germinal centers late in the primary response, providing activated B-cells the ability to produce antigen-specific antibodies of differing isotypes. Heavy chain constant regions are isotype-specific and distinguish the 5 isotypes (IgM, IgG, IgA, IgE, and IgD), while the variable regions are antigen-specific. Light chains are antigen- specific and do not determine isotype. Isotype switching first requires interaction of the CD40 receptor on activated B-cells with the CD40 ligand (CD154) expressed by activated T-cells. Afterward, isotype switching can occur through genetic rearrangement of the heavy chain constant regions. This process is modulated by T- cell cytokines such as IL-2, IL-4, IL-5, IL-6, and IFN-y. After the primary immune response, subsequent encounters with the same antigen generate a predominantly IgG response (or IgA in the case of a mucosal response).
The process of negative selection in T cell maturation is essential for eliminating T cells that bind to self MHC or self antigens with overly high affinity.
This process occurs in the thymic medulla.
T-Helper cell differentiation