B cells PDF

B cells Learning Objectives On completion of this session you should be able to 1) Describe the function of B cells in the adaptive immune response, including antibody production and antigen presentation. 2) Explain the clonal selection theory. 3) Understand the mechanisms underlying the gen...

B cells Learning Objectives On completion of this session you should be able to 1) Describe the function of B cells in the adaptive immune response, including antibody production and antigen presentation. 2) Explain the clonal selection theory. 3) Understand the mechanisms underlying the generation of antibody diversity. Adaptive Response 1) Commences ~96 h after initial infection 2) Initiated if innate system fails to contain and eliminate infectious agents 3) Mediated by B & T lymphocytes 4) B cells – mediate adaptive humoral response 5) B cells -> antibody (plasma cells) 6) T cells – mediate adaptive cell mediated response 7) T cells -> Tc, Th1, Th2, TFH, Th17 8) Activation of adaptive immunity occurs in secondary lymphatic tissue (Lymph nodes, spleen, MALT) Adaptive Response – Clonal Selection Theory 1. Each lymphocyte bears a single type of receptor of unique specificity 2. Interaction between foreign antigen and lymphocyte receptor leads to lymphocyte activation 3. Activated lymphocytes proliferate clonally and differentiate into effector cells which bear antigen receptors of identical specificity to those of the parent cell 4. Lymphocytes bearing receptors specific for self molecules are deleted at an early stage in lymphoid cell development and are absent from the repertoire of mature lymphocytes B Cells 1) B lymphocytes function in the humoral immunity component of adaptive immune system producing antibodies (plasma cells) 2) Each kind of B cell produce one kind of antibody 3) Memory (memory cells) 4) Antigen specificity 5) Discrimination between self and non-self B Cells 1) 3 types: B1 cells – found in the peritoneal and pleural cavities Marginal zone B cells – found in marginal zone of spleen Follicular B cells – found in B cell follicles in lymphatic tissue Generation of Diversity 1) Each B cell synthesises antibody with unique specificity 2) The collection of antibody specificities is called the antibody repertoire and is approx 1011 in humans 3) For each specificity to be encoded by a separate gene is inefficient 4) Diversity arises due to processes of somatic gene recombination and somatic hypermutation Somatic Gene Recombination 1) DNA encoding V and C regions is separated in all cells except B cells 2) During development, coding segments are brought together so a functional antibody molecule can be produced 3) This occurs for both H and L chain genes Light Chain Genes: 4) Two light chain genes encoding k and l chains 5) k Light chain genes are found on chromosome 2 Somatic Gene Recombination 1) l Light chain genes are found on chromosome 22 2) The light chain V region is encoded by DNA formed from the recombination of two gene segments - a V (variable) gene segment - a J (joining) gene segment 3) The V gene segment encodes the first 95 - 101 amino acids and the J gene segment encodes for the remainder of the domain (~13 residues) Somatic Gene Recombination 1) The V region DNA is separated from the C region DNA by non-coding sequences that are removed by RNA splicing to give the mature RNA transcript 2) For k light chain genes there are ~38 V gene segments and 5 J gene segments 3) Potentially 190 different Vk regions can be produced 4) For l light chain genes there are ~30 V gene segments and 4 J gene segments 5) Potentially 120 possible Vl regions can be produced Somatic Gene Recombination 1) C region coding sequences are located downstream and joined by RNA splicing 2) Heavy chain genes comprise ~40 V gene segments, 23 D gene segments and 6 J gene segments 3) Potentially ~5,520 different VH regions can be produced 4) Combining H and L chains, ~1.7 x 106 different antibody specificities can be produced Additional Mechanisms for Diversity 1. Imprecise joining of segments: Nucleotides can be added or deleted during the joining of segments in a random manner B cells with non-functional rearrangements are deleted 2. Somatic Hypermutation: Occurs in secondary lymphoid organs Point mutations are introduced in V-regions of rearranged H- and L-chain genes This results in the production of high affinity antibody during an immune response Summary 1. B cells are key players in the adaptive immune response, fulfilling crucial roles in antibody production and antigen presentation. 2. They are central to the clonal selection theory, which proposes that antigen-specific B cells are selectively activated and expanded upon encountering their cognate antigen. This theory underpins our understanding of how the immune system responds to diverse pathogens. 3. The generation of antibody diversity is facilitated by mechanisms such as somatic hypermutation, ensuring a broad repertoire of antibodies capable of recognising various antigens.