Antigen-specific IGG2A production in response to prostaglandin E2, immune complexes, and IFN-γ

Sidney Stein, Richard P. Phipps

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Immune complexes (IC) can inhibit the differentiation of B lymphocytes into IgM secreting plasma cells in both Ag-specific and polyclonal systems. This report describes the ability of IC and IFN-γ, or IFN-γ and PGE2 to regulate the class of Ig produced in an Ag-specific system. In an in vitro model system using fluorescein (FL)-Brucella abortus as Ag, we previously showed that IC composed of an anti-FL antibody and FL-Ag inhibited the ability of FL-specific B cells to develop into IgM plaque-forming cells. In addition, PGE2 sensitized resting B cells to IC, whereas pretreatment with IL-4 alleviated the IC-mediated decrease in the IgM anti-FL response. In this manuscript, we demonstrate that IFN-γ has antagonistic effects compared to IL-4, and potentiates the IC-induced decrease in the IgM antibody response. Interestingly, we discovered that the virtual ablation of the anti-FL IgM response exhibited by B cells treated with IC and IFN-γ was accompanied by a dramatic increase in the anti-FL IgG2a response. Furthermore, resting B lymphocytes pulsed with IFN-γ and PGE2, but not PGF2α, exhibited augmented IgG2a production. This effect was also observed when IFN-γ-pulsed B cells were stimulated with other agents, such as dibutyryl cAMP and cholera toxin, that elevate intracellular levels of cAMP. In addition, RpcAMP, the R-isomer of a sulfur-modified cAMP and a cAMP antagonist, inhibited antiFL IgG2a responses. The ability of cAMP elevators such as PGE2 to promote IgG2a production, as well as to increase the frequency of IgG2a secreting cells, was demonstrated in B lymphocytes treated with IFN-γ and polyclonally activated by LPS. Overall, our results demonstrate that IFN-γ and PGE2-treated B lymphocytes challenged with antigen or LPS generate elevated levels of IgG2a via a cAMP-dependent pathway. These observations suggest that in vivo, PGE2 secreted by cells such as macrophages potentiates the ability of IFN-γ to promote an IgG2a response, the predominant murine antiviral Ig.

Original languageEnglish (US)
Pages (from-to)2500-2506
Number of pages7
JournalJournal of Immunology
Volume147
Issue number8
StatePublished - Oct 15 1991
Externally publishedYes

Fingerprint

Antigen-Antibody Complex
Dinoprostone
Fluorescein
B-Lymphocytes
Antigens
Immunoglobulin M
Interleukin-4
Elevators and Escalators
Brucella abortus
Dinoprost
Cholera Toxin
Plasma Cells
Sulfur
Antibody Formation
Antiviral Agents
Anti-Idiotypic Antibodies
Macrophages

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Antigen-specific IGG2A production in response to prostaglandin E2, immune complexes, and IFN-γ. / Stein, Sidney; Phipps, Richard P.

In: Journal of Immunology, Vol. 147, No. 8, 15.10.1991, p. 2500-2506.

Research output: Contribution to journalArticle

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abstract = "Immune complexes (IC) can inhibit the differentiation of B lymphocytes into IgM secreting plasma cells in both Ag-specific and polyclonal systems. This report describes the ability of IC and IFN-γ, or IFN-γ and PGE2 to regulate the class of Ig produced in an Ag-specific system. In an in vitro model system using fluorescein (FL)-Brucella abortus as Ag, we previously showed that IC composed of an anti-FL antibody and FL-Ag inhibited the ability of FL-specific B cells to develop into IgM plaque-forming cells. In addition, PGE2 sensitized resting B cells to IC, whereas pretreatment with IL-4 alleviated the IC-mediated decrease in the IgM anti-FL response. In this manuscript, we demonstrate that IFN-γ has antagonistic effects compared to IL-4, and potentiates the IC-induced decrease in the IgM antibody response. Interestingly, we discovered that the virtual ablation of the anti-FL IgM response exhibited by B cells treated with IC and IFN-γ was accompanied by a dramatic increase in the anti-FL IgG2a response. Furthermore, resting B lymphocytes pulsed with IFN-γ and PGE2, but not PGF2α, exhibited augmented IgG2a production. This effect was also observed when IFN-γ-pulsed B cells were stimulated with other agents, such as dibutyryl cAMP and cholera toxin, that elevate intracellular levels of cAMP. In addition, RpcAMP, the R-isomer of a sulfur-modified cAMP and a cAMP antagonist, inhibited antiFL IgG2a responses. The ability of cAMP elevators such as PGE2 to promote IgG2a production, as well as to increase the frequency of IgG2a secreting cells, was demonstrated in B lymphocytes treated with IFN-γ and polyclonally activated by LPS. Overall, our results demonstrate that IFN-γ and PGE2-treated B lymphocytes challenged with antigen or LPS generate elevated levels of IgG2a via a cAMP-dependent pathway. These observations suggest that in vivo, PGE2 secreted by cells such as macrophages potentiates the ability of IFN-γ to promote an IgG2a response, the predominant murine antiviral Ig.",
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