A fourth heavy chain variable region subgroup, w, with 2 variants defined by an induced auto-antiserum in the rabbit.

An antiserum recognizing previously undescribed antigenic determinants (designated subgroup w) of the heavy chain VH region was produced by immunizing a rabbit, homozygous for the VH haplotype a1x-y- with IgG from another a1x-y- rabbit, suppressed for a1. The antiserum gives a single fused precipitin band against sera from homozygous rabbits suppressed for the a1, a2, or a3 allotypes. By gel diffusion analysis, the determinant was found to be distinct from previously described a, x, and y allotypes, and was detectable on IgG, F(ab')2 gamma and the gamma-heavy chain. Radioinhibition analysis revealed 2 patterns of inhibition suggesting 2 variants of w that are closely linked to VH allotypes. Variant w34 was detected at very low levels (0.042 to 5.6 micrograms/mg IgG) in normal rabbits expressing the a1x-y-, a1-y33,30, and a3x32y- VH haplotypes. Variant w35 was detectable in a 2x32y33,- rabbits. Sera from homozygous a allotype-suppressed rabbits representing each of the 4 VH haplotypes similarly exhibited either w34 or w35 patterns of inhibition as described above. The level of w34 in a1- and a3-suppressed rabbits exhibited a dramatic 230-fold median increase. In contrast, w35 levels for a2-suppressed rabbits fell within the normal range. In addition to reacting with essentially all normal and suppressed sera, the antiserum reacted with preimmune serum from the same rabbit. Thus, anti-w represents an induced auto-antibody. These observations are further discussed with regard to rabbit and mouse VH populations.