EXPRESSION OF AN ANTI-DNA-ASSOCIATED V-H GENE IN IMMUNIZED AND AUTOIMMUNE MICE

The j558 family BW-16 V-H gene is closely associated with the autoimmu ne response to DNA, of luprus-prone mice, We have followed the express ion of VHBW-16-encoded heavy chains in cDNA libraries prepared from un manipulated normal (C3H, AKR) and autoimmune (New Zealand Black/New Ze aland White F-1) mice, and from mice immunized with a highly immunogen ic peptide/DNA complex. The prevalence, clonal heterogeneity, and stru ctural properties (somatic mutation, complementarity-determining regio n 3 composition) of these H chains were investigated, and the DNA affi nity of VHBW-16-encoded hybridoma mAb was measured in solution, We fin d that H chains encoded by VHBW-16 are very rare in Igs of normal mice , but increase significantly in peptide/DNA-immunized mice, and dramat ically in diseased mice, The experimentally induced VHBW-16-encoded H chains are clonally restricted, somatically mutated, partly switched f rom IgM to IgG, and give rise to anti-DNA Abs with low affinity, in co ntrast, the VHBW-16-encoded H chains from diseased New Zealand Black/N ew Zealand White mice are clonally heterogeneous, exclusively of the I gG isotype, and produce high affinity anti-DNA autoantibodies, We conc lude that the experimentally induced and spontaneous immune responses to DNA are qualitatively similar, but quantitatively different, and ma y truly reflect the principles of self immunologic tolerance.