Ans: A (Somat.), C (DNA..) & D (Appro..) Gene switching (tor class switching) is also observed in formation of lg. The primary immune response is the formation of IgM immunoglobulin. This is followed by secondary immune response in formation of IgG immunoglobulin" - Chatterjea &Shinde 7th/258Ig Gene Rearrangement and Expression# As a cell differentiates into a mature B cell that will make a light chain, there is a rearrangement of the various genes (exons) and the gene begins to be expressedThe orderly sequence nf rearrangements in the immunoglobulin gene families explains;Why an individual B celi can only produce one kind of immunoglobulin with one kind of heavy and one kind of light chain.Why a individual B cell can only make antibodies of one specificity.Why there is allelic exclusion in immunoglobulin allotypes at the level of an individual immunoglobulin molecule but codominant expression of allotypes in the organism as a whole.Antibody diversityRefers to the sum total of all the possible antibody specificities that an organism can make, it is estimated that we can make 107 - 108 different antibody molecules. One of the major questions in immunology has been how can we make so many different antibody molecules.Theories which have attempted to explain the origin of antibody diversity fall into two major categories.Germ line theory: This theory states that we have a different V region gene for each possible antibody we can make.Somatic mutation theory :This theory states that we have only one or a few V region genes and the diversity is generated by somatic mutations which occur in these genesIt is thought that antibody diversity is generated by the following mechanisms1 A large number of V genesThere are:a) 30 lambda V genes; b) 300 kappa V genes; c) 1000 heavy chain V genes2 V-J and V-D-J joiningThe region where the light chain :V gene and J region or the heavy chain V gene and D and J regions come together is in the third hypervariable region. Since it is random which V and which J or D regions come together, there is a lot of diversity that can be generated by V-J 3nd V-D-J joining.3 Junctional diversity (Inaccuracies in V-J and V-D and D-J recombinationRecombination between V-J and V-D-J is not always perfect and additional diversity can arise by errors that occur in the recombination event that brings the V region next to the J or D regions or the D region next to the J region. It is estimated that these inaccuracies can triple the diversity generated by V-J and V-D-J joining. The diversity generated by this4 N region insertionAt the junction between D and J segments there is often an insertion of a series of nucleotides which is catalyzed by the enzyme terminal transferase. Terminal transferase catalyzes the random polymerization of nucleotides into DMA without the need for a template. This leads to further diversity' in the third hypervariable region.5 Somatic MutationThere is evidence that somatic mutations are occurring in the V gene, particularly in the place that codes for the second hypervariable region. Thus, somatic mutation probably contributes to antibody diversity to some extent.6 Combinatorial AssociationAny individual B cell has the potential to make anyone of the possible heavy chai ns and any one of the possible light chains. Thus, different combinations of heavy and light chains within an individual B cell adds further diversity.7 MultispecificityDue to cross reactions between antigenic determinants of similar structure an antibody can often react with more than one antigenic determinant. This is termed multispecificity. Multispecificity also contributes to antibody diversityB Cell Receptor (Immunoglobulin) HeavyKappaV gene segments1000300D gene segments15-| gene segments44N region insertion++-Junctional diversity++++Somatic mutation++Combinatorial associationV x D x J1000 X 15 X 4V x J300x4Total6 x 1041.2 x 103Combinatorial association7.2 xl07