B-cell Function and Characterisatics:B cells comprise approximately 35 percent of the circulating lymphcytes and primarily are responsible

for humoral immunity (i.e., production of specific serum immunoglobulins directed against various environmental antigens).B cells function in antibody production in two distinct ways. In the first and clearly most simple case, antigens bind directly to the B cells surface; B cells then undergo a clonal proliferation followed by terminal differentiation into plasma cells. Plasma cells are highly specialized for the secretion of immunoglobulins. In the second and more complex case, antigens are bound to the surface immunoglobulins of helper T cells. Next, these antigen-antibody complexes are released from helper T cells and bound to macrophages. Finally, the B cells interact specifically with stimulated macrophages and subsequently undergo a clonal proliferation and plasma cell differentiation. Certain B cells persist after initial exposure to an antigen and exist in the form of memory B cells. These cells can undergo a rapid clonal expansion if a person is exposed again, even years later, to the same antigen. B cells are most heavily concentrated in the germinal centers of aggregates of lymphoid tissue. For example, B cells are found in large numbers in the cortical aggregates in lymph nodes and in the white pulp of the spleen. T cell development: Fetal stem cells are destined to become T cells, which enter the thymus and proliferate there. These immature T cells (called thymocytes while in the thymus for the periphery as mature T cells). During T cell development in the thymus, several changes occur. 1. Some type of selection process occurs, which favors the proliferation of thymocytes that are restricted by self-MHC molecules. That is, thymocytes are selected for their ability to recognize antigens associated with molecules of the same MHC type. 2. Precursors of both helper T (Th) cells (MHC class II-restricted) and cytotoxic T (Tc) lymphocyte (MHC class I- restricted) are selected. 3. Current evidence suggests that cortical thymic epithelial cells, which express both class I and class II MHC glycoproteins are important in this selection event; the mechanism is still unknown. General Characteristics of T cells: a. T cell surface markers: 1. Monoclonal antibody techniques have identified molecules on the T cell membrane that function chiefly as receptors. 2. These surface molecules include: a. Class I and class II MHC molecules b. Thy 1, Ly1, Ly2,3 and L3T4 in mice. c. CD (cluster of differentiation) antigens (e.g., CD3, CD4, and CD8) in humans.

3. As a thymocyte differentiates toward a particular T cell subtype, it acquires certain CD antigens in its membrane and loses others. Thus, the T cell subsets can be distinguished by their CD markers. 4. CD3, CD2, and CD5 are found on most peripheral blood T cells. a. CD3 is a heteropolymer with at least five polypeptide chains; it appears late in differentiation when the cells are becoming immunocompetent. i. CD3 is associated with the T cell receptor for antigen and it is important in intracellular signaling to initiate an immune response once the cell has interacted with a homologous epitope. ii. CD3 is not directly involved in antigen recognition, but antibodies against CD3 will block the antigen-specific activation of T cells. b. CD2 (the SRBC receptor) is responsible for resetting of sheep red blood cells (SRBCs) in the E-rosette assay for T cell enumeration. c. CD5 is expressed on all T cells and on a subset of B cells that appear to be predisposed to autoantibody production. 5. CD4 and CD8 are present on different effector T cells and on a subset of B cells that appear to be predisposed to autoantibody production. 6. Antiserum against certain of the membrane markers (e.g., against CD3) is immunosuppressive and has been used to prevent rejection of transplanted tissues. b. The T cell receptor for antigen 1. T cell have an antigen-specific receptor that functions as the antigen recognition site. This surface component , the T cell receptor (TCR), bears significant structural homology with the Fab portion of an antibody molecule. 2. Structure and Function of TCR: a. The TCR is a heterodimer. i. It consists of two nonidentical polypeptide chains, an chain (about 45kDa) and a chain (about 40 kDa), linked together by disulfide bonds. ii. Both chains of the heterodimer are variable; there may be more variability in the smaller () chain. b. The TCR contains idiotypic determinants similar to those of immunoglobulin molecules. Hypervariability occurs in particular areas of each polypeptide chain in a manner analogous to the complementarity-determining regions (CDRs) of immunoglobulin molecules. c. The TCR heterodimer is noncovalently linked in the T cell membrane to the ,, and chains of the CD3 molecule. d. The TCR-CD3 complex apparently makes contact with both the antigen and a portion of the MHC molecule. Different portions of the hypervariable regions of the and chains interact with:

i. The helical sides of the epitope-binding cleft of the MHC molecule. ii. The epitope lying on the floor of the cleft. e. CD4 or CD8 molecules (depending on the T cell subset) also contact a portion of the MHC molecule.