Tuesday, June 23, 2020

B Cell Receptor and Antiboby Production



Anything that is non-self or foreign to the body is considered as  antigens.  Once antigens enter our body, lymphocytes produce specific immunological reactions against the antigens in order to remove them and to prevent the development of  an infection or disease due to that particular antigen. This immune response can be humoral or cell mediated. Humoral immune response results in the production of antibodies (Ab) by B lymphocytes. Cell-mediated immunity does not involve antibodies. Rather, it involves antigen-specific cytotoxic T-lymphocytes, the activation of phagocytes and the release of various cytokines in response to antigen.
Antigens (An) are usually  bacteria, bacterial products, fungi, viruses or other parasites.  Entire organisms  usually do not function as the antigen. Particular macromolecules of these infectious agents usually act as antigens. Proteins are the major antigens and polysaccharides coming next to it. Lipids and nucleic acids of these microorganisms do not act as antigens unless they are coupled with proteins or polysaccharides.  Antigens are also called antibody generators as they induce the immune system to produce antibodies. Hence, Antibodies are glycoproteins produced in response to  antigens by the host immune system whose function is to eliminate the entered antigen. 
In order to produce antibodies, first the antigen should activate the B lymphocytes. Activated B cells are called Plasma cells or Plasma B cells.  Plasma cells are white blood cells that could secrete large volumes of antibodies or immunoglobulins. These secreted immunoglobulins are transported by blood plasma and lymphatic system to destroy the entered antigens. 
The B cells, a type of white blood cells, are produced by multipotent hematopoietic stem cells (HSCs) in the bone marrow.  Mature B-cells that have not been exposed to antigens are called naive B cells.



Naive B cells carry special receptors on their cell membrane to which the An binds. These receptors are called B Cell Receptors or BCRs. BCRs are made up of two parts. First part is the transmembrane antibody attached to the cell membrane of the B cell, to which the  antigen binds. Antibodies of  any one isotype like IgD, IgM, IgA, IgG, or IgE are acting as BCRs.  These antibodies are also called membrane immunoglobulin (mIg). This region is oriented outward, away from the cell. The second part is the signal transduction transmembrane heterodimer proteins embedded in the cell membrane of B cells called Igα & Igβ. These heterodimers are held together by disulfide bonds. The transmembrane immunoglobulin and the heterodimer proteins together make up the so called BCRs. 
Each individual B cell has around 50,000 BCRs on its surface. But one B cell carries BCRs specific for only one particular antigen. Thus, the B cell population of an adult individual carries BCRs for as many as 10 13    different antigens. Means 10 13   different and undifferentiated B cells are present in an adult human body. They circulate in blood, awaiting the activation by specific antigen. 



When an An is captured, the membrane receptor communicates with the nucleus through the signal transduction heterodimer proteins and B Cell is activated. Upon activation,  these B-cells immediately undergo clonal proliferation and differentiate into antibody producing plasma cells (effector B cells) and memory cells.  Plasma cells will secrete soluble antibodies and these Abs circulate through the bloodstream to identify the antigen that had induced its synthesis.  Such circulating antibodies are also present in the serum, tissue fluid and mucosal surfaces of vertebrates. Memory cells remain in circulation for very longer periods and produce secondary response. When the same An enters the body for a second time, memory cells  proliferate and differentiate into plasma cells, which then clear the antigen.


                                                    Image Courtesy: immunology.org




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