Characteristics and regulatory function of murine con A-induced, cloned T cells obtained from Peyer's patches and spleen: mechanisms regulating isotype-specific immunoglobulin production by Peyer's patch B cells.

Abstract

Abstract To determine the role of T cells in the regulation of IgA responses by murine PP B cells, Con A-induced T cell clones and subclones derived from PP and spleen were established. The cloned and subcloned cell lines obtained were radioresistant (1500 R) and expressed Thy-1.2+, Lyt-1+2−, H-2 (K/D), and la (l-A and l-E) surface antigens. The cloned T cells proliferated to T cell mitogens (Con A and PHA), but not to a B cell mitogen (LPS). In addition, the Con A-induced cloned and subcloned T cells bore class-specific Fc receptors but in an organ-specific fashion: T cell clones and subclones derived from PP, but not from spleen, bore IgA and (to a lesser extent) IgM Fc receptors. The capacity of the cloned and subcloned T cells to regulate polyclonal immunoglobulin (Ig) synthesis by PP B cells induced by LPS was determined. LPS in the absence of T cells induced abundant amounts of IgM and IgG, but little or no IgA. The addition of cloned or subcloned T cells derived from PP profoundly suppressed production of IgM and IgG, whereas they enhanced IgA synthesis to a limited degree. In contrast, although cloned and subcloned T cells derived from spleen also suppressed IgG synthesis, they had no effect on IgM synthesis; as in the case of the PP cloned and subcloned T cells, the spleen clones and subclones provide modest help for IgA synthesis. In the absence of LPS stimulation, cloned and subcloned T cells from both PP and spleen exerted minimal help to all classes of Ig secretion by PP B cells. Finally, changes in surface Ig in LPS-driven cell cultures containing cloned T cells were determined. Cultures containing cloned T cells had nearly the same number of B cells at the end of the culture period as cultures without cloned T cells. In the presence of PP T cell clones, cells bearing surface IgM (slgM) decreased to some extent, cells bearing slgG and containing cytoplasmic IgM (clgM) and IgG (clgG) decreased dramatically, and cells bearing slgA increased dramatically. In contrast, in the presence of spleen T cell clones, no significant changes in IgM- or IgA-bearing or -containing cells were observed, but IgG-bearing ceils increased and IgG-containing cells decreased. These results are compatible with the view that the cloned T cells derived from PP, but not from spleen, induce Ig class switching of B cells to slgA-bearing B cells, but cannot in themselves provide help for terminal differentiation of IgA B cells.