Antibodies are the secreted form of the B-cell receptor. An antibody is identical to the B-cell receptor of the cell that secretes it except for a small portion of the C-terminus of the heavy-chain constant region. In the case of the B-cell receptor the C-terminus is a hydrophobic membrane-anchoring sequence, and in the case of antibody it is a hydrophilic sequence that allows secretion. Since they are soluble, and secreted in large quantities, antibodies are easily obtainable and easily studied. For this reason, most of what we know about the B-cell receptor comes from the study of antibodies.

Antibody molecules are roughly Y-shaped molecules consisting of three equal-sized portions, loosely connected by a flexible tether. All antibodies are constructed in the same way from paired heavy and light polypeptide chains, and the generic term immunoglobulin is used for all such proteins. Within this general category, however, five different classes of immunoglobulin--IgM, IgD, IgG, IgA, and IgE--can be distinguished by their C regions. More subtle differences confined to the V region account for the specificity of antigen binding. The most variable regions of the antibody structure are the CDRs (CDR1, CDR2 and CDR3) which are in contact with the antigen. CDR1 and CDR2 are encoded by the V gene segment whilst CDR3 lies at the junction of V and J segments in the light chain and is partly encoded by the D segment in the heavy chain. It is observed that the germline diversity for CDR2 is much higher than that of CDR1. Diversity is introduced into the CDR3 loop by random addition of p-nucleotides and N-nucleotides at the segment joints. Nucleotides can also be deleted at the segment junctions by exonucleases thereby adding to the variation and further altering the length of the CDR3 loop.

The CDR3 loop is the most variable in sequence as well as structure due to these diversity introducing mechanisms. Further variation is introduced by somatic hypermuation which introduces point mutations at various hotspots in the V region. This process occurs in B-cells after they encounter an antigen. Mutations undergo selection process known as affinity maturation. Most of the mutations which result in base changes are concentrated in the CDR regions whilst silent mutations are present throughout the V region. Mutational hotspots are thought to be concentrated in the CDR1 region as it has the least amount of germline diversity. Mutational hotspots have also been reported in the framework region away from the CDRs and are thought to create minor changes in the conformation and alter the antigen binding properties.

These variations increase the receptor repertoire and also alter affinity and specificity of the antibody molecule. Mutations that disrupt the antibody structure or compromise its binding capacity are selected against.

The hydrophobic amino acids (I, V, L, F, C, M, A) and Tryptophan (W) which were found in more than 50% of the analysed Immunoglobulin molecules at the same position. Most of them are part of the framework regions and are involved in the protein folding and disulphide bond formation which provides structural stability to the antibody molecule.

There are many databases to understand the antibody structure and also get a clear picture of its constant and variable regions. One such one is IMGT which stands for 'The international ImMunoGeneTics information system®.' B-cell differentiation and antibody production is a highly coordinated process which has evolved to create numerous antigen recognition molecules with high specificity and affinity to almost any antigenic molecule. The system has installed various checkpoints to ensure efficient and accurate working of our defence mechanisms.

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