Mitogenic Properties of Fab and F(ab′)2 Fragments of Rabbit Anti‐Human β2‐Microglobulin for Human Lymphocytes

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Abstract
Bivalent F(ab'')2 fragments and monovalent Fab fragments of rabbit anti-human .beta.2-microglobulin (anti-.beta.2m) stimulated DNA synthesis in human lymphocytes. Mitogenicity of anti-.beta.2m antibodies can 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-.beta.2m IgG was comparable to that obtained with the original IgG antibodies when tested at the same protein concentration. Since Fab monomers of anti-.beta.2m can cause lymphocyte activation, cross-linking of hypothetical .beta.2-microglobulin-containing lymphocyte receptors does not seem necessary for activation. F(ab'')2 and Fab fragments of anti-.beta.2m blocked the cytotoxic effect of anti-.beta.2m IgG, showing that the fragments did indeed react with .beta.2-microglobulin on the cell surface. F(ab'')2 dimers, but not Fab monomers, of anti-.beta.2m were capable of inhibiting the cytotoxic effect of an anti-HLA-A2 antiserum. The mitogenic activity of anti-.beta.2m IgG and Fab monomers of such antibodies disappeared after absorption with highly purified .beta.2-microglobulin. The mitogenic effect of anti-.beta.2m 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.