Class-specific suppression of human B cell maturation by IgA-binding factors.

IgA-binding factors (IgA-BFs) were prepared by chromatography on Sepharose 4B beads covalently linked to dimeric and polymeric monoclonal IgA1 from supernatants of peripheral blood mononuclear lymphocytes (PBMC) and human B cell lines incubated in serum-free medium. Receptors for IgA, as revealed by the binding of biotinylated monoclonal IgA1, were expressed on monocytes, T-enriched and T-depleted lymphocytes. IgA-BFs or control eluates were added to pokeweed mitogen (PWM)-stimulated PBMC cultures, and their effects on the terminal differentiation of polyclonally activated human B cells were assessed by enumeration of intracytoplasmic IgM-, IgG- or IgA-containing cells. A selective decrease of IgA-containing cells was observed in the presence of IgA-BFs whereas IgM- and IgG-containing cells remained unchanged. Differential counts of B blasts and plasma cells revealed that only the former were decreased following addition of IgA-BFs. Kinetic studies indicated that maximum inhibition of IgA-containing cell generation was achieved when IgA-BFs were added during the first 5 days of PWM-stimulated PBMC cultures, whereas no inhibition could be demonstrated when IgA-BFs were added 24 h before harvesting. IgA-BFs did not decrease [3H]thymidine incorporation in PWM-stimulated PBMC cultures. They diminished the proliferation of the surface IgA+ monoclonal human B cell line DAKIKI, but not that of the surface IgA- IM-9 cell line. Several control eluates obtained from the same cell supernatants absorbed on Sepharose 4B, Sepharose 4B-IgG or Sepharose 4B-beta 2-microglobulin had no effect. Finally, IgA-BFs prepared from supernatants of two human B cell lines bearing receptors for IgA selectively depressed the generation of intracytoplasmic IgA+ cells in PBMC cultures stimulated by PWM. Altogether the data indicate that IgA-BFs obtained by spontaneous release from heterogeneous mononuclear cell suspensions or from IgA receptor-positive human monoclonal B cell lines selectively depress the maturation of B cells into IgA plasma cells and the proliferation of a surface IgA+ B cell line.