Major Steps in the Differentiation of T And B Lymphocytes

MAJOR STEPS IN THE DIFFERENTIATION OF T AND B LYMPHOCYTES

The differentiation of T and B lymphocytes proceeds in major three stages.

A. Gene Rearrangement

The tremendous diversity and specificity of the immune system is mediated by antigen spe-cific receptors expressed on the surface of the T and B cells, the T-cell receptor (TcR), and surface-bound immunoglobulins, which constitute the B-cell receptor (BcR), respectively. Diversity is accomplished by the combining of rearranged genes encoding variable (V), di-versity (D), joining (J), and constant (C) regions .

B. Association with Co-receptors

The TcR and BcR are members of the immunoglobulin gene superfamily, display similar macromolecular structures, and associate with homologous co-receptors. The antigen-spe-cific binding site of each receptor resides within its immunoglobulin-like domains. The short intracytoplasmic regions of these antigen recognition receptors are not capable signal transduction. The TcR and BcR associate in the cytoplasm with other molecules, forming receptor complexes, which are then transported to the cell membrane. The co-receptor molecules lend signal transduction capacity to the mature receptor complex. Events that precipitate gene rearrangement, synthesis of antigen receptors, and co-receptor association proceed in a sequential manner and are dependent on activating signals received from the environment.

C. Selection of the Right Receptors

Because of its random nature, the rearrangements of receptor genes, which become ex-pressed on the surface of differentiating lymphocytes, may include autoreactive receptors.

A selection process exists to eliminate autoreactive lymphocytes, which would react against self-antigens.