SPECIFICITIES AND GENETIC-CHARACTERISTICS OF NUCLEOSOME-REACTIVE ANTIBODIES FROM AUTOIMMUNE MICE

Antinuclear antibodies are present in the serum of individuals with sy stemic autoimmune diseases such as SLE. Most autoantibodies characteri zed to date are directed against isolated nuclear molecules such as DN A or histones. We have obtained from spontaneously autoimmune mice six IgG mAb that recognize conformational nucleosome epitopes, but do not react with individual histones or DNA. For three of these mAb, the ep itope is at least partially present in the H2A-H2B-DNA nucleosome subp article, although their binding characteristics differ from those of c onventional anti-H2A-H2B-DNA antibodies. All six mAb use V-H or V-kapp a genes which are recurrently utilized in anti-DNA and other antinucle ar antibodies. The V regions of the nucleosome-reactive mAb also conta in charged (mostly cationic) residues at sites that are likely to be c ritical for interaction with nucleosomal antigens. These results sugge st that the usage of certain V gene segments in conjunction with suita ble V(D)J rearrangements may confer reactivity to nucleosomal antigens . B cells producing such autoantibodies are probably expanded early du ring the autoimmune process. Somatic mutations in the V regions of nuc leosome-reactive mAb may modulate their specificities and result in th e acquisition of binding patterns restricted to individual chromatin c omponents such as DNA.