BALB/c immunized with adjuvant (CFA) only. light chain as 2C3, and bind both phthalate and ds and ss-DNA. They specifically recognize the oligonucleotides, d(pT)4, Caerulomycin A and d(pT)10. Additionally, when antisera raised against idiopeptides corresponding to 2C3-Ig hypervariable regions are allowed to react with 2C3-Ig, their binding is blocked specifically by Caerulomycin A both d(pT)4 and phthalate. This study clearly demonstrates that phthalate exposure leads to activation of a significant number of autoreactive B-cells, with the consequence of a significant pathogenic progression in susceptible NZB/W F1 mice but not in non-autoimmune-prone BALB/c. == Introduction == The aetiology of autoimmune disorders such as induction of anti-DNA antibodies in systemic lupus erythematosus (SLE) is largely unknown. High titres of anti-double-stranded (ds) DNA antibodies have been considered as the serological hallmark of a systemic autoimmune disease like lupus.1,2Anti-DNA JAK3 antibodies in lupus-prone mice undergo heavy chain class switching to immunoglobulin G (IgG), and display somatic mutations in their variable region gene segments.3,4The structure of variable regions of anti-DNA antibodies indicates that they are produced in response to antigen-selective stimulation.5 Various environmental, genetic, and hormonal antigenic factors have been implicated in the development of this disease.68Some studies have implied that molecular mimicry between self and microbial antigens could play a role in triggering production of autoreactive anti-DNA antibody.9It is possible that activation of self-reactive clones of T or B cells may also occur during exposure to chemicals that are abundantly present in the environment or administered as medications.10,11 Phthalates (i.e.o-benzene dicarboxylates) comprise one such group of chemicals that are widely used as plasticizers in flexible polyvinyl chloride (PVC) polymers used in medical devices, children’s toys, and as solvents for cosmetics. Another type of phthalate is widely used in making synthetic fibres. Thus, phthalate compounds in various forms readily occur in day-to-day human contacts. In rodents, these chemicals have often proved harmful,1215although there is as yet no report linking phthalates to autoimmune disorders. The present study was initiated during our studies with an anti-phthalate monoclonal antibody (mAb), 2C3-Ig.16It was noted from a search in the BLAST database of National Center for Biotechnology Information (NCBI) that the amino acid sequence of 2C3-Ig chain variable regions has extensive homology (>98%) with that of BV04-01, an auto anti-DNA mAb from autoimmune-prone NZB/W F1 mice. The homology between the two with respect to heavy chain variable regions is less striking (70%). Indeed, both 2C3 and BV04-01 are cross-reactive with single and double-stranded DNA and have specific affinity for d(pT)4 oligonucleotides.17This finding led us to determine if phthalates elicit an autoreactive antibody response, particularly anti-self DNA antibody responses in BALB/c, NZB and autoimmune-prone Caerulomycin A NZB/W F1 mice. It appears that phthalatekeyhole limpet haemocyanin (KLH) immunization evokes complex immune responses that include anti-DNA antibodies in all these mice, but not so in KLH-immunized control mice. Analysis, at the clonal level using hybridomas from the fusion of phthalate-KLH primed BALB/c splenocytes, reveals that these hybridomas exhibit significant cross-reactivity towards phthalate, and DNA. This finding strongly indicates that phthalate as a conjugate with KLH is capable of inducing antibodies specific not only for the hapten itself but also for DNA, especially, against d(pT)4 oligonucleotides. However, repeated exposure to phthalate affects only the NZB/W F1 mice in terms of mortality. To our knowledge, this is the first report implicating a commercially used chemical phthalate in the induction of autoreactive immune response in.