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Effects of type I/type II interferons and transforming growth factor‐β on B‐cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression
Author(s) -
D. Mark Estes,
Wenbin Tuo,
Wendy C. Brown,
Juan Carlos Goin
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00645.x
Subject(s) - biology , breakpoint cluster region , immunoglobulin class switching , cytokine , antibody , cd40 , immunology , b cell , endogeny , interferon gamma , immunoglobulin g , pokeweed mitogen , receptor , endocrinology , concanavalin a , cytotoxic t cell , in vitro , biochemistry
In this report, we sought to determine the role of selected type I interferons [interferon‐α (IFN‐α) and interferon‐τ (IFN‐τ)], IFN‐γ and transforming growth factor‐β (TGF‐β) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B‐cell receptor (BCR) cross‐linking. IFN‐α enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN‐α than dual cross‐linking with CD40. Recombinant ovine IFN‐τ was less effective at inducing IgG2 responses when compared with IFN‐α, though IgA responses were similar in magnitude following BCR cross‐linking. At higher concentrations, IFN‐τ enhanced IgA responses greater than twofold over the levels observed with IFN‐α. Previous studies have shown that addition of IFN‐γ to BCR or pokeweed mitogen‐activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN‐γ was relatively ineffective 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‐β on immunoglobulin synthesis by bovine B cells. Exogenous TGF‐β stimulates both IgG2 and IgA production following CD40 and BCR cross‐linking in the presence of IL‐2. Blocking endogenous TGF‐β did not inhibit the up‐regulation of IgG2 or IgA by interferons.