B and T Lymphocytes Utilize Similar Mechanisms To Generate Diversity in Antigen Receptors

Antigen Is Recognized Differently by B and T Lymphocytes

Antigens, which are generally very large and complex, are not recognized in their entirety by lymphocytes. Instead, both B and T lymphocytes recognize discrete sites on the antigen called antigenic determinants, or epitopes. Epitopes are the immunologically active regions on a complex antigen, the regions that actually bind to B-cell or T-cell receptors.

Although B cells can recognize an epitope alone, T cells can recognize an epitope only when it is associated with an MHC molecule on the surface of a self-cell (either an antigen-presenting cell or an altered self-cell). Each branch of the immune system is therefore uniquely suited to recognize antigen in a different milieu. The humoral branch (B cells) recognizes an enormous variety of epitopes: those displayed on the surfaces of bacteria or viral particles, as well as those displayed on soluble proteins, glycoproteins, polysaccharides, or lipopolysaccharides that have been released from invading pathogens. The cell-mediated branch (T cells) recognizes protein epitopes displayed together with MHC molecules on self-cells, including altered self-cells such as virus-infected self-cells and cancerous cells.

Thus, four related but distinct cell-membrane molecules are responsible for antigen recognition by the immune system:

- Membrane-bound antibodies on B cells

- T-cell receptors

- Class I MHC molecules

- Class II MHC molecules

Each of these molecules plays a unique role in antigen recognition, ensuring that the immune system can recognize and respond to the different types of antigen that it encounters.

The antigenic specificity of each B cell is determined by the membrane-bound antigen-binding receptor (i.e., antibody) expressed by the cell. As a B cell matures in the bone marrow, its specificity is created by random rearrangements of a series of gene segments that encode the antibody molecule. As a result of this process, each mature B cell possesses a single functional gene encoding the antibody heavy chain and a single functional gene encoding the antibody light chain; the cell therefore synthesizes and displays antibody with one specificity on its membrane. All antibody molecules on a given B lymphocyte have identical specificity, giving each B lymphocyte, and the clone of daughter cells to which it gives rise, a distinct specificity for a single epitope on an antigen. The mature B lymphocyte is therefore said to be antigenically committed.

The random gene rearrangements during B-cell maturation in the bone marrow generate an enormous number of different antigenic specificities. The resulting B-cell population, which consists of individual B cells each expressing a unique antibody, is estimated to exhibit collectively more than 10¹⁰ different antigenic specificities. The enormous diversity in the mature B-cell population is later reduced by a selection process in the bone marrow that eliminates any B cells with membrane-bound antibody that recognizes selfcomponents. The selection process helps to ensure that selfreactive antibodies (auto-antibodies) are not produced.

The attributes of specificity and diversity also characterize the antigen-binding T-cell receptor (TCR) on T cells. As in B cell maturation, the process of T-cell maturation includes random rearrangements of a series of gene segments that encode the cell’s antigen-binding receptor. Each T lymphocyte cell expresses about 10⁵ receptors, and all of the receptors on the cell and its clonal progeny have identical specificity for antigen. The random rearrangement of the TCR genes is capable of generating on the order of 10⁹ unique antigenic specificities. This enormous potential diversity is later diminished through a selection process in the thymus that eliminates any T cell with self-reactive receptors and ensures that only T cells with receptors capable of recognizing antigen associated with MHC molecules will be able to mature.

Дата добавления: 2014-01-11