Isotype-specific immunoregulation. IgA-binding factors produced by Fc alpha receptor-positive T cell hybridomas regulate IgA responses

Abstract

T-T hybridomas, produced by fusions between R1.1 T lymphoma and cloned T helper cells that promote IgA responses (Th A cells) were characterized in this study. A total of 85 cloned cell lines were produced, and their supernatants were assessed for support of antigen-dependent IgA (and IgM and IgG) responses. 16 of 85 culture fractions supported IgA anti-sheep red blood cell, -horse red blood cell, or -trinitrophenyl responses in either lipopolysaccharide-triggered splenic B cell, or normal Peyer's patch B cell cultures, and the responses were specific for the antigen used for in vitro immunization. None of the supernatants from the cell lines induced significant polyclonal responses in these B cell cultures. Interestingly, the 16 hybridomas that produced supernatants with IgA-promoting properties had Fc receptors for IgA (Fc alpha R), but did not express Fc mu R or Fc gamma R. When supernatants from Fc alpha R+ T cell lines were subjected to IgA affinity chromatography, the IgA-promoting activity bound to IgA (IBF alpha) and was recovered in the eluate. No binding of active fractions occurred when supernates were passed through IgM or IgG immunoadsorbent columns. High concentrations of purified IBF alpha suppressed T-dependent IgA responses, while an optimal level was required for enhancement of this isotype response. These results suggest that Fc alpha R+ hybridomas derived from Th A cells release IBF alpha into the culture medium, and that these molecules regulate IgA responses to various T-dependent antigens.