Differentiation of B cells in the bovine. Role of cytokines in immunoglobulin isotype expression

Abstract

Cytokines such as IFN-γ, IL-4 and TGF-β, are known to regulate Ig class switching by positively or negatively regulating germline C H transcription in the mouse and human. Here we show at the protein level that similar regulatory mechanisms are in place in the bovine using various modes of B cell activation and cytokine combinations. Using antigen-receptor cross-linkage or mitogen (pokeweed mitogen) costimulation, we demonstrate that recombinant bovine IL-4 upregulates the expression of IgM, IgG 1 and IgE in vitro. Upregulation of IgG 1 and IgE production by rboIL-4 is inhibited in a dose-dependent manner by the addition or rboIFN-γ to the cultures. Using similar methodologies, we have also investigated the effects of TGB-β on IgA production in the presence or absence of various cofactors including IL-10 and IL-2. We find that TGF-β will not solely upregulate IgA production from noncommitted precursors (sIgM +) in coculture with mitogen or with formalin fixed Staphylococcus cowan Strain I (SAC), but does have positive effects on IgA production in the presence of both IL-2 and IL-10. These observations suggest that different modes of T-independent costimulation using classical B cell activators does not result in differential IgG subisotype or IgE production by bovine B cells in the presence of cytokines. Together these results suggest that individual cytokines regulate isotype expression in cattle.