Immunology
The rearrangement of T cell receptor (TCR) genes g and d occur in series of cells expressing variable Vg and Vd gene segments. The lymphoid precursor cells originate in the bone marrow and move to the thymus. Preliminary T cells are devoid of TCR, CD4 and CD8 molecules and are called double negative thymocytes . These double negative T cells may be further categorized into four phases of differentiation (DN1, CD44+CD25-; DN2, CD44+CD25+; DN3, CD44-CD25+; and DN4, CD44-CD25-) . CD44 is a cell adhesion molecule and CD25 serves as the IL-2 receptor. Passage into the DN2 and DN4 stages causes expression of pre-TCR and consequent cell proliferation during DN4, leading to the double-positive switch and substitution of the pre-TCR -chain with the rearranged TCR--chain, generating the entire a-b TCR. The double-negative T cells either switch off the -chain gene expression and commit to the cell lineage, or switch off the and chain gene expression and commit the T cell towards cell lineage.
T CELL ACTIVATION
On encountering the antigenic peptides on the Antigen presenting cells, TCR in combination with CD3 complexes strongly to the complex of peptide-MHC Class II. These physical interactions trigger the activation and phosphorylation of the intracellular kinase proteins occurring on the TCR, CD3 and the co-receptor CD4. In the next phase, co-stimulatory molecules CD 28 are activated and a confirmation step occurs to ensure that the TCR recognizes only foreign antigens and are not autoreactive. After these signals are processed, the TH-2 (T-helper) cell further proliferates following secretion of the cytokine IL-2, which functions in an autocrine manner.
ANTIBODY CLASS SWITCH IN B-CELLS
In the course of development, many B cells transition from producing a particular category of antibody to another, a mechanism termed as class switching . All B cells initiate their antibody-producing action by making IgM molecules, introducing them into the plasma membrane and acting as receptors for antigen. Prior to encountering an antigen, many B cells switch and produce primary antibodies IgM and IgD that serve as membrane-attached antigen receptors. Antigen-driven class switch begins with exposure to antigen and cells that causes some B cells to get activated and release IgM antibodies that take over the primary antibody response . Other antigen-stimulated cells transition to producing secondary antibodies IgG, IgE, or IgA. In this process, memory cells express any one of these classes of antibodies on their cell surface, while activated B cells release them. The class switching occurs by a specific assembled VH segment serially interacting with a variable CH gene segment. With the plethora of antigens encountered by the immune system, it is crucial for the immune system to divide the functional roles of combating these antigens. Hence, different types of antibody isotypes occur that are specialized in their biological functions, locations and their capacity to handle a wide range of antigens.
B-CELL ACTIVATION
Binding of antigen to the B cell receptor (BCR), the antigen gets endocytosed by receptor-mediated endocytosis, processed and then combined with MHC II molecules occurring on the surface of the B cell . The second signal emanates from the association of the B cell with the TCR on the T helper cells, which activates the B cell, causing their proliferation. The activation of the naïve B cells involves formation of germinal centers and plasma cells. The gene expression and functioning of these cells are regulated by transcriptional factors Bcl6, Bach2 and Blimp1 .
Works Cited
Alberts, B et. al. Molecilar Bilogy of the cell. Garland Publishing, 2002.
Germain, R. "T-cell development and the CD4–CD8 lineage decision." Nature Reviews Immunology (2002): 2, 309-322.
Janeway, C. Immunobiology. Garland Science, 2008.
Ochiai, K. "Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4." Immunity (2013): 38 (5): 918-929.
R&Dsystems. B cell Activation. 2016. <https://www.rndsystems.com/research-area/b-cell-activation>.
Alberts, B et. al. Molecilar Bilogy of the cell. Garland Publishing, 2002.
Germain, R. "T-cell development and the CD4–CD8 lineage decision." Nature Reviews Immunology (2002): 2, 309-322.
Janeway, C. Immunobiology. Garland Science, 2008.
Ochiai, K. "Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4." Immunity (2013): 38 (5): 918-929.
R&Dsystems. B cell Activation. 2016. <https://www.rndsystems.com/research-area/b-cell-activation>.
