Somatic diversification of immunoglobulins.

A series of three IgM, kappa monoclonal antibodies arising from a fusion of BALB/c spleen cells from mice immunized with beta-(1,6)-galactan-containing antigens have been analyzed. These three lines were found (i) to have homologous protein sequences in the heavy chain D region and at the sites of recombination between the heavy chain variable and D segment (VH-D) and the D and joining segment (D-JH), although amino acid substitutions were observed in both the heavy and light chain variable regions; (ii) to use identical heavy and light chain joining segments; and (iii) to demonstrate two identical (productive and nonproductive) kappa-chain rearrangements. A likely explanation for these observations is that the three lines are clonally related (arise from a common precursor) and that the observed heavy and light chain variable segment substitutions represent somatic point mutations. Because these antibodies are all of the IgM class, the results indicate that a somatic mutational mechanism is activated early in B-cell ontogeny and operates at both the heavy and light chain loci. Furthermore, the somatic mutation process appears to continue during the development of a given cell line, but is independent of class switching.