NORMAL HUMAN CORD-BLOOD B-CELLS CAN PRODUCE HIGH-AFFINITY IGG ANTIBODIES TO DSDNA THAT ARE RECOGNIZED BY CORD BLOOD-DERIVED ANTIIDIOTYPIC ANTIBODIES

It is possible to identify, in Epstein-Barr virus-transformed normal h uman cord blood B cell populations, cells present at a low frequency t hat produce IgG antibodies specific for dsDNA. By cloning out these B cells as immortalized monoclonal cell lines, it could be shown that th e antibodies were the products of CD5 positive B cells. Two monoclonal anti-dsDNA antibodies were derived from cell lines T52 and A7 and the se were further characterized as anionic (PI similar to 6.4) IgG4 kapp a antibodies that bound with affinities of 7.18 x 10(9) l/mol and 3.28 x 10(9) l/mol, respectively, to dsDNA but did not bind to ssDNA. Thes e affinities were similar to those of polyclonal IgG anti-dsDNA antibo dies from lupus patients, which ranged from 1 x 10(9)-8.9 x 10(10) l/m ol. Both T52 and A7 monoclonal anti-dsDNA antibodies were recognized b y cord blood-derived IgM antibodies. These IgM antibodies were not rhe umatoid factors but bound to the F(ab')2 of A7 and T52 while failing t o recognize T50, which is an autologous IgG4 kappa monoclonal antibody without specificity for dsDNA. A cloned B cell line A24 generated fro m the same cord blood sample as A7 produced an IgM monoclonal antibody that bound to the heavy chains of T52 and A7, but not T50 on Western blot and inhibited the binding of these antibodies to dsDNA. A7 and T5 2 competitively inhibited each other in their binding to the antiidiot ype A24, and A24 inhibited the binding to dsDNA of some polyclonal IgG anti-dsDNA. antibodies purified from sera of lupus patients. The leve l of inhibition of binding of these antibodies to dsDNA was directly p roportional to the levels of expression of the idiotype recognized by A24 on these antibodies. The normal human cord blood, therefore, may c ontain cells that form an idiotype/anti-idiotype network in which the idiotype is expressed on IgG antibodies with specificity for dsDNA and the anti-idiotype is an IgM antibody that binds to a heavy chain idio tope in such a way as to interfere with its interaction with dsDNA. Th e presence of a similar idiotype on some polyclonal anti-dsDNA antibod ies in lupus that are similarly inhibitable by the cord blood-derived anti-idiotype raises the possibility that this network may persist in later life and perhaps become dysfunctional in systemic lupus erythema tosus.