Mitogenic properties of Fab and F(ab')2 fragments of rabbit anti-human beta2-microglobulin for human lymphocytes.

Bivalent F(ab')2 fragments and monovalent Fab fragments of rabbit anti-human beta2-microglobulin (anti-beta2m) stimulated DNA synthesis in human lymphocytes. Mitogenicity of anti-beta2m antibodies can therefore be ascribed to the antigen-binding site and not to the Fc portion of the molecule. The mitogenic response to F(ab')2, and sometimes Fab, fragments of anti-beta2m IgG was comparable to that obtained with original IgG antibodies when tested at the same protein concentration. Since Fab monomers of anti-beta2m can cause lymphocyte activation, 'cross-linking' of hypothetical beta2-microblobulin-containing lymphocyte receptors does not seem necessary for activation. F(ab')2, as well as Fab, fragments of anti-beta2m blocked the cytotoxic effect of anti-beta2m IgG, showing that the fragments did indeed react with beta2-microblobulin on the cell surface. F(ab')2 dimers, but not Fab monomers, of anti-beta2m were capable of inhibiting the cytotoxic effect of an anti-HLA-A2 antiserum. The mitogenic activity of both anti-beta2m IgG and Fab monomers of such antibodies disappeared after absorption with highly purified beta2-microblobulin. The mitogenic effect of anti-beta2m IgG was inhibited to a minor extent by exposure of cells to high concentrations of pooled multispecific anti-HLA antibodies. This effect was probably nonspecific.