Polyclonal IgA secretion is inducible in murine B cells when DC-T from Peyer's patches (PP) provide the inducing stimulus. PP DC-T, which are composed predominantly of dendritic cells and Lyt-1+ T cells, are capable of dramatic augmentation of IgA secretion by PP or spleen B cells with minimal induction of IgM secretion. DC-T from spleen, however, are incapable of augmenting IgA secretion by either PP or spleen B cells. The level of IgA secretion is dependent upon the dose of DC-T providing the inducing stimulus and reaches a plateau with DC-T:B ratios of less than 1:1. This system for preferential induction of IgA responses should permit elucidation of cellular mechanisms involved in regulation of IgA secretion.

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.

In this review, we have emphasized: 1) bacterial lipopolysaccharide (LPS) involvement in IgA responses to orally administered thymic-dependent (TD) antigens; 2) characterization of Peyer's patch (PP) lymphoreticular cells; and 3) gastrointestinal immunization with gram negative pathogens and anti-LPS immunity to infection. Gut LPS, which interacts with PP lymphoreticular cells, is a major determinant for host responses to orally administered TD antigens. Bacteroides species are the principal microflora present in the gastrointestinal tract and our studies with phenol-water LPS extracts from Bacteroides fragilis indicate that both polysaccharide and lipid A activate lymphoreticular cells. The B. fragilis lipid A moiety, like that derived from E. coli and Salmonella LPS, induces B cell mitogenic responses in cultures from LPS responsive mice, but does not stimulate C3H/ H3J B cells. The inability of lipid A to stimulate gut-associated lymphoreticular tissue (GALT) cells of C3H/HeJ mice results in the induction of greater T helper cell activity in this tissue in response to orally administered TD antigens and ultimately results in an elevated IgA response pattern. Murine PP contain accessory cells (approximately 1% dendritic cells and 6-8% macrophages) and lymphocytes T (35-38%) and B (40-42%). Recent studies with antigen-specific T cell clones from C3H/ H3J PP have resulted in the isolation of IgA isotype-specific T helper cells (PP Th A cells). PP Th A cells are antigen-specific, bear Fc alpha receptors, and require H-2 histocompatibility with B cells for helper activity. PP Th A cells most effectively collaborate with surface IgA (sIgA)-bearing B cells (IgA committed B cells) for IgA isotype responses. Other studies have shown that PP dendritic cells and T cells form clusters when stimulated in vitro with sodium periodate and that these clusters promote polyclonal IgA responses in B cell cultures. Polyclonal IgA responses in cultures containing PP cell clusters from C3H/ H3J mice are considerably higher than those in identical cultures from LPS responsive mice. In other studies, the environmental influence on GALT B cells and their resultant commitment to IgA isotype is under investigation. CBA/N, X-linked immunodeficient (xid) mice possess an immature splenic B cell population which cannot respond to thymic-independent class-2 (TI-2) or certain TD antigens. However, GALT B cells of xid mice possess a mature Lyb-5+ B cell subpopulation capable of both TI-2 and TD responses.(ABSTRACT TRUNCATED AT 400 WORDS)

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