F. Monneaux et al., Murine models of systemic lupus erythematosus: B and T cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F-1 lupus mice, INT IMMUNOL, 13(9), 2001, pp. 1155-1163
(NZB x NZW)F-1 and MRL/Fas(Ipr) lupus mice present a similar phenotype with
a spectrum of autoantibodies associated with very severe nephritis. It is
thought, however, that in contrast to other lupus-prone mice such as MRL/Fa
s(Ipr) mice, (NZB x NZW)F-1 mice do not generate autoantibodies to ribonucl
eoproteins (RNP) Sm/RNP. In this study, we demonstrate that contrary to pre
vious reports, the autoimmune response directed against Sm/RNP antigens als
o occurs in NZB x NZW mice. CD4(+) T cells from unprimed 10-week-old NZB x
NZW mice proliferate and secrete IL-2 in response to peptide 131-151 of the
U1-70K protein, which is known to contain a T-h epitope recognized by CD4 T cells from MRL/Fas(Ipr) mice. Peptide 131-151, which was found to bind I
-A(k) and I-E-k class II MHC molecules, also bound both I-A(d) and I-E-d mo
lecules. This result led us to also re-evaluate longitudinally the anti-Sm/
RNP antibody response in NZB x NZW mice. We found that 25-week-old mice do
produce antibodies reacting with several small nuclear and heterogeneous nu
clear (hn) RNP proteins, such as SmD1, Ul-70K and hnRNP A2/B1 proteins. The
fine specificity of these antibodies was studied with overlapping syntheti
c peptides. The same antigenically positive and negative peptides were char
acterized in MRL/Fas(Ipr) and NZB x NZW mice in the three proteins. This ne
w finding can help to understand the mechanisms involved in the development
of the anti-Sm/RNP antibody response and, particularly, the role played by
non-MHC genes in this autoimmune response.