DNA Antibody Production Research Articles

Effects of UV Radiation on Autoimmune Strains of Mice: Increased Mortality and Accelerated Autoimmunity in BXSB Male Mice

Systemic lupus erythematosus is an immunologically mediated autoimmune disease which has been reported to be aggravated by certain environmental agents such as ultraviolet irradiation (UV). To further investigate this interaction, we examined the consequences of UV exposure on the autoimmune process of several strains of autoimmune mice. Strains of age- and sex-matched, 3- to 4-month old, autoimmune (MRL-lpr/lpr, (NZB X NZW)F1, BXSB) and nonautoimmune (BALB/c, B10.A) mice were shaved and exposed to an acute (2 h daily X 7 days) and a chronic (3 h/weekly X 4 weeks) dose of UV (FS40 lamps, 2 mJ/cm2/s). UV-induced changes in survival, autoantibody production, splenic B-cell activity, and target organ pathology were examined. After an acute UV exposure there were (10/15) deaths in the UV BXSB males and (4/15) in the UV BXSB females, compared to (1/15) in the non-UV BXSB male group and (0/15) in the non-UV BXSB females. No deaths occurred in the other UV autoimmune or nonautoimmune groups. Likewise, chronic UV resulted in increased UV BXSB male mortality (13/15) compared to UV BXSB females (2/15) and non-UV BXSB males and females. No deaths occurred in the other autoimmune (MRL-lpr/lpr, (NZB X NZW)F1) or nonautoimmune (BALB/c, B10.A) strains, after chronic UV exposure. Equivalent doses of Mylar-filtered FS40 UV (UVB deleted) resulted in no deaths in the UV BXSB male group. Acute and chronic UV also resulted in a significant increase in serum single-stranded DNA antibody production, splenic polyclonal B-cell activity, and renal glomerular inflammatory changes in the UV BXSB male mice. Thus, UV resulted in premature death and accelerated autoimmunity in UV BXSB males and may serve as a useful model for phototoxicity in autoimmunity.

Anti DNA antibody production by lymphoid cells of [formula omitted] mice and human systemic lupus erythematosus (SLE)

Single-stranded DNA (S-DNA) coupled to sheep erythrocytes by the chromic chloride method was used to detect antibody-producing cells by a standard hemolytic plaque assay (PFC), and antigen sensitive rosette-forming cells (RFC) by the technique of immunocytoadherence. The spleens and other lymphoid tissue of 6–10-month-old NZB W F 1 female mice were studied. The spleens of these mice showed anti-S-DNA antibody-producing cells, which reached a peak in the 7–9-month-old mice, and correlated directly with the magnitude of the serum antiS-DNA antibody detected by the Farr assay. Studies of human lymphoid cells from bone marrow and peripheral blood of patients with systemic lupus erythematosus (SLE) also revealed significant numbers of anti-S-DNA PFC's.

ANTIBODIES TO DNA AND A SYNTHETIC POLYDEOXYRIBONUCLEOTIDE PRODUCED BY OLIGODEOXYRIBONUCLEOTIDES.

Calf-thymus DNA was degraded into small fragments (oligodeoxyribonucleotides); the fragments were treated with methylated bovine serum albumin, and the complexes so formed were emulsified in complete Freund's adjuvant and injected into rabbits. The serums of the immunized rabbits contained antibodies that reacted with homologous and heterologous unfragmented heat-denatured DNA, and also with a synthetic polydeoxyadenylate-thymidylate. Relatively small DNA fragments (of the order of tetra-hexanucleotide) can thus serve as haptens for the production of DNA antibodies; this finding increases the probability of producing antibodies specific for unique sequences of nucleotides.