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Antibodies Secreted by B lymphocytes Great diversity and specificity: 109 different antibodies; can distinguish between very similar molecules Tag particles for clearance/destruction Protect against re-infection (vaccines) Antibody Structure The Immunoglobulin Superfamily(a few examples) Antibody Classes: Structure Affinity and Avidity Affinity and Avidity II Monoclonal Antibodies Single antibody (all same H and L chains) Made by fusion of B cells to a transformed cell line of the plasma cell type and selection for “hybridomas” that produce antibody with the desired properties Standardized, unlimited reagent for diagnosis or therapy (human antibodies or “humanized” antibodies can be made) Generation of Monoclonal Antibodies Monoclonal antibodies used in medicine Generation of antibody diversity How do we make 109 different antibodies? Genes for antibodies are present in pieces that can be combined in many different combinations in different lymphocytes V region of Ig L and H chains are constructed from 2 and 3 different pieces each having multiple copies V(D)Jrecombination Generation of Antibody Diversity k light chains: 40 Vk x 5 Jk = 200 l light chains: 30 Vl x 4 Jl = 120 H chains: 40 VH x 27 DH x 6JH = 6,480 320 L chains x 6,480 H chains = 2.1 x 106 Junctional diversity (addition or deletion of nucleotides at recombination sites, especially of H chain), estimated to add 3x107 fold to overall diversity Discovery of Rag1, 2 genes Mechanism of V(D)J recombination Creation of Junctional Diversityby P-regions and TdT Defects in Lymphocyte development leading to severe combined immunodeficiency (SCID) Lymphoid malignancies resulting from errors in V(D)J recombination Proposed mechanism of targeting of somatic hypermutation Activation-induced cytidine deaminase (AID) Discovered as an induced gene in a cell line with inducible class-switch recombination (subtractive hybridization) Transfection into B cell lines induces class switch recombination AID KO mice have str