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Background  HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65 336-439  instigates autoimmunity, suggesting that pp65 336-439  contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65 422-439  for immunization of BALB/c mice and mapping of B cell epitope.    Methods  The target epitope pp65 422-439  reactivity and B cell epitope mapping was examined in serum from pp65 422-439 -immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis.    Results  Anti-pp65 422-439  antibody in serum either from patients with SLE or from pp65 422-439 -immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65 422-439 -immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65 422-439 -derived decapeptides, one dominant epitope, pp65 428-437 , was identified in serum from pp65 422-439 -immunized mice and patients with SLE with anti-pp65 422-439  antibody. Epitope spreading from pp65 428-437  to pp65 430-439  was found in pp65 422-439 -immunized mice in which we generated monoclonal antibodies to pp65 425-434  and pp65 430-439 . However, dsDNA positive reactivity was exclusively observed in  Crithidia luciliae  stains with pp65 430-439 -reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65 428-437.Conclusions  Our data suggest that pp65 428-437  may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.    Electronic supplementary material  The online version of this article (doi:10.1186/s13075-017-1268-2) contains supplementary material, which is available to authorized users.

B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice