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.

Proinflammatory cytokines regulate FcαR expression by human mesangial cells in vitro

“…The R1.1 (mouse lymphoma) cell line, negative for FcaR [37], was purchased from the American Type Culture Collection (ATCC, Rockville, MD) and maintained in Dulbecco's modified Eagle's medium supplemented with 10% horse serum. The human monocytic cell line U937, a kind gift from Dr M. L. Tykocinski (Case Western Reserve University, Cleveland, OH), was maintained in RPMI 1640 supplemented with 10% fetal bovine serum (FBS).…”

Con A-Propagated, Auto-Reactive T Cell Clones that Secrete Factors Promoting High IgA Responses

“…The relevant PP T cells could, for example, require PP-derived accessory cells during their propagation rather than the splenic accessory cells with which we provided them: PP T cells that functioned in promoting especially high IgA responses by secreting an IgA-binding factor [11,24] might well be more successfully propagated, or their ability to make the binding factor more successfully maintained, in the presence of PP B cells producing IgA. In the work cited, the T cell clones that spontane ously expressed Fc«R and secreted IgA-binding fac tor were, however, like ours, propagated in the pres ence of irradiated spleen cells rather than PP cells.…”

Peyer’s Patches: Organized Lymphoid Structures for the Induction of Mucosal Immune Responses in the Intestine

“…Kiyono et al [148,149] and Mayer et al [150,151] found that murine antigen-specific T cell clones derive from PP specifically expanded sIgA + B cells but not sIgA -B cells via an IgA-binding factor. Benson and Strobber [152] addressed the question of T cell regulation of B cell isotype differentiation by using a non-neoplastic human tissue source.…”