B-Cell Receptors (BCRs)

• Cell receptors and their soluble form, antibodies, and T cell receptors are glycoproteins.
• Glycoproteins are in each person in an amount that far exceeds the diversity of pathogens.
• Each receptor recognizes only one pathogen.
• Billions of types of receptors work to recognize every pathogen.

B Cell Receptor

• A symmetric molecule comprised of 4 protein chains: 2 light chains and 2 heavy chains.
• Chains consist of constant and variable sequence domains.
• Light chain: 1 variable + 1 constant domain.
• Heavy chain: 3 or 4 constant + 1 variable domain.
• Chains connect via disulfide bridges formed between cysteine amino acids.
• The B cell receptor has a Y-shaped structure.
• Variable domains at the ends of the forks create the antigen binding site.
• The stem of the Y-shaped structure is the constant domain, which provides spatial stability and certain effector functions.
• Based on constant domain variability, the 5 main types of heavy chains are IgM, IgD, IgG, IgA, and IgE.
• There are 2 types of light chains: κ and λ.
• The receptor has two identical antigen-binding sites, enabling bivalent interaction with the appropriate antigen.

BCR vs Soluble Form

• BCR is located on the surface of B cells.
• BCR has a transmembrane region.
• BCR is associated with other membrane-anchored signaling chains, which transmit activating signals to the cell.
• The soluble form is produced by plasma cells
• The soluble form secreted by the cells into the extracellular space
• Structurally identical to the cell surface immunoglobulin molecule
• Recognizes the same antigen as the original BCR.
• Lacks the transmembrane region, so it does not connect to a signaling chain.

T Cell Receptor (TCR)

• Structurally similar to the antibody molecule
• The antigen-recognizing part consists of two chains
• Each chain comprises one constant domain and one variable domain
• Disulfide bridges form between cysteine amino acids within and between the chains
• Two variable domains are responsible for recognizing the antigen/MHC-peptide complex
• Constant domains stabilize structure
• Has a membrane-anchoring region
• Covalently linked to the signaling chain
• Only one antigen-binding site
• A soluble form does not form

Clonal Division of B Cells

• In the bone marrow, 10 million to 1 billion B cells are formed daily.
• Naive B lymphocytes create antibodies through gene translocation, resulting in antibodies that have a unique antigen-binding site (Fab).
• Antibody molecules are presented on the surface of B cells as B cell receptors, capable of reacting with the epitopes of an antigen.
• Unique antigen-recognizing receptors with distinct specificities are expressed on the cell surface.
• Each lymphocyte displays approximately 100,000 receptors, but each has the same specificity.
• This means that a single cell is specialized to recognize only one type of antigen.
• Lymphocytes that recognize their own structures with high "intensity" are destroyed in the early phase.
• This prevents self-recognizing autoimmune lymphocytes from entering the periphery, a process known as central tolerance.
• After maturation in primary immune organs, they enter the bloodstream and exit into secondary lymphoid organs to search for antigens.
• If they do not encounter their specific antigen, they continue migrating through the lymphatic and circulatory systems to other lymph nodes/secondary lymphoid tissues, checking their antigen repertoire.
• B lymphocytes encounter foreign antigens in secondary lymphoid tissues.
• Foreign substances that enter the peripheral lymphoid organs interact with the lymphocyte repertoire that entered the circulation from the bone marrow.
• Epitopes of the antigen ultimately react with those B lymphocytes whose surface B cell receptors fit them well.
• This interaction activates these B lymphocytes
• This process is called clonal selection.
• Cytokines produced by effector T helper (T4) lymphocytes facilitate the rapid proliferation of activated B lymphocytes, resulting in the formation of a clone consisting of thousands of identical B lymphocytes.
• During proliferation, they also undergo affinity maturation, which results from somatic hypermutations.
• Affinity maturation allows B lymphocytes to refine the shape of their antibodies to better fit the original epitope.
• B lymphocytes with surface B cell receptors that fit better bind to the epitope for a longer time and more tightly, enabling these cells to replicate selectively.
• B lymphocytes differentiate into antibody-producing plasma cells, which secrete a massive amount of antibodies that fit the original epitope.
• Some B lymphocytes differentiate into B memory cells, which can mount an anamnestic response.
• Activated naive B lymphocytes take about 4-5 days to complete clonal expansion and differentiate into an effector B lymphocyte.
• A single activated B lymphocyte can generate approximately 4,000 antibody-producing cells within a week.
• A plasma cell can produce more than 2,000 antibody molecules per second.
• Once the pathogen is destroyed, the disappearance of the antigen renders the pathogen-specific clones redundant, leading to their destruction by apoptosis in the final stage of the immune response.

Clonal Division of T Cells

• Part 1 : The T cell receptor encounters an antigen-presenting cell (APC) that presents a fragment of the pathogen on its cell surface, then TCR recognizes the specific antigen presented by the APC.
• Part 2 : TCR specifically binds to an antigen, activating the T cell.
• Part 3 : Activated T cell undergoes rapid division, producing numerous clones possessing the original T cell's specific TCR.
• During clonal division, two types of T cells are generated: Effector and Memory T Cells.
• Effector T Cells are directly involved in combating the infection.
  • CD8+ cytotoxic T cells destroy infected cells.
  • CD4+ helper T cells activate other immune cells.
• Memory T Cells will remain in the body for a long time and respond more quickly if the same infection reappears, which in turn provides immunological memory.
• After a successful infection elimination, apoptosis occurs in the effector T cells
• The memory cells remain, ready for another infection.

Explore B-cell receptor structure, function, and antigen-binding specificity. Understand the role of heavy and light chains, constant and variable regions, and effector functions associated with different antibody isotypes. Learn how BCRs mediate immune responses.