Effects of type I type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression

In this report, we sought to determine the role of selected type I interfer ons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-Rho (TGF-Rho) in the regulation of bovine an tibody responses. B cells were stimulated via CD40 in the presence or absen ce of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-l inking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were simi lar in magnitude following BCR cross-linking. At higher concentrations, IFN -tau enhanced IgA responses greater than twofold over the levels observed w ith IFN-alpha. Previous studies have shown that addition of IFN-gamma to BC R or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffec tive at stimulating high-rate synthesis of any non-IgM isotype. Dual cross- linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2. and IgA production following CD40 and BCR c ross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.