The avian immune system exhibits a unique immunoglobulin (Ig) system characterized by distinct features absent in other vertebrates. Birds possess a specialized IgY, which serves as the functional equivalent to mammalian IgG and IgE, but with significant structural and functional differences. Unlike mammalian systems, birds utilize a limited number of germline gene segments and rely on gene conversion within the bursa of Fabricius to generate antibody diversity. This mechanism allows for a rapid and diverse immune response, showcasing the evolutionary adaptation of birds to their ecological niches and pathogen challenges.

The 12/23 rule is fundamental in the V(D)J recombination process, which assembles the variable (V), diversity (D), and joining (J) gene segments in the immune system to create diverse antibodies and T cell receptors. The rule stipulates that recombination can only occur between a gene segment flanked by a recombination signal sequence (RSS) with a 12-base pair (bp) spacer and one with a 23-bp spacer. This ensures proper alignment and prevents inappropriate recombination, thereby maintaining the integrity and functionality of the immune response​.

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