The Clonal Nature of Antibody Formation

Abstract Antibody cell clones of (C57BL/6 C3H/HeJ) F1 mice directed against the haptens, poly-O-acetyl-d-serine (poly-ser) and poly-d-alanine (poly-ala), were evaluated with the aid of a cell transfer system and a modified plaque assay. When antibody responses to poly-ser or poly-ala were initiated by a few precursor cells, unequal associations of a given antibody specificity with one of two parental antibody allotypes became apparent: namely, poly-ser specific clones of C3H/HeJ allotype were more frequent than those of C57BL/6 allotype, whereas poly-ala specific clones of C57BL/6 allotype were more frequent than those of C3H/HeJ allotype. The degree of these unequal associations could be accentuated when both poly-ser and poly-ala specific clones were induced with proteins bearing random copolymers of O-acetyl-d-serine and d-alanine (ser-ala). In this instance the proportion of clones which were of C57BL/6 allotype was greater than that obtained with either homopolymer hapten. We interpreted these results as consistent with the following: 1) that closely-linked genes encoded for the two distinct portions of mouse immunoglobulin heavy-chain that determine allotype (constant region) and combining site specificity (variable region); and 2) that more of the immunoglobulin structural genes of the C3H/HeJ allelic chromosomal region could encode for antibodies to the poly-ser hapten than those of the C57BL/6 allelic chromosomal region, while the converse seemed true for antibodies specific to the poly-ala hapten.