Lack of heterogeneity in anti-hapten antibodies of a phylogenetically primitive shark

Abstract

Individual mammals have the capacity to express at least one million distinct antigen binding specificities, implying a high degree of structural heterogeneity in the variable H and L chain (VH and VL) portions of the antibody molecules. This heterogeneity probably is created through a sizeable repertoire of germ-line VH and VL genes and through random rearrangements of V and joining genes. Additional somatic mechanisms probably contribute to the ultimate heterogeneity; 1/3 of murine plasmacytomas producing .gamma.1 Ig carry a somatically mutated Ig1-V gene. The relative contributions of these various mechanisms to the overall Ig variability are difficult to evaluate. The production of different antibodies to a defined determinant in different individuals of an inbred mouse strain [e.g., (3-iodo-4-hydroxy-5-nitrophenyl) acetyl (NIP) in CBA mice] suggests the involvement of somatic mutations or rearrangement, but does not rule out the possibility that each individual CBA mouse expresses only a small random fraction from a large germ-line repertoire of V genes determining different anti-NIP binding sites. The opposite finding, that different individuals produce nearly identical antibodies to a defined determinant, would suggest the presence and expression of a limited number of germ-line genes without somatic alterations. Primitive sharks (H. francisci) probably produce such antibodies to the hapten furyloxazolone.