Class‐specific suppression of human b cell maturation by iga‐binding factors

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Abstract
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‐β2‐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.

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