We have recently demonstrated that pharmacological agents that elevated cAMP inhibited sigM but not Lyb2 mediated activation of murine B lymphocytes. In this report we show evidence for differential regulation of prostagiandin E2 (PGE2), a physiological agent that elevated cAMP and IFN-γ on sigM and Lyb2 mediated B cell activation. PGE2 inhibited anti-lgM but not anti-Lyb2 induced DNA synthesis in a dose-dependent manner. Interestingly, rlFN-γ also inhibited anti-lgM but not anti-Lyb2 induced DNA synthesis. rlFN-γ exerted its effects directly on B cells since depletion of T cells and G-10 Sephadex adherent cells did not alter effects of IFN-γ on anti-lgM and anti-Lyb2 induced DNA synthesis. Pretreatment of B cells with IL-4 and/or IL-5 didnot prevent the IFN-γ mediated inhibition of the anti-lgM response. The inhibitory effect of IFN-γ was observed during early stages of B cell activation. Thus IFN-γ inhibited anti-μ induced blast transformation and subsequent progression into the G1 phase of the cell cycle. The differential effects exerted by PGE2 and rIFN-γ appeared to be mediated by distinct mechanisms.Thus PGE2 but not rIFN-γ, at concentrations inhibitory to the slgM response, induced elevation of intracellular cAMP levels. These results demonstrate that physiologically relevant immunomodulators such as PGE2 and IFN-γ can differentially regulate murine B cell responses mediated through the antigen receptor and Lyb2 molecules by cAMP dependent and independent mechanisms. Relevance of this regulation for the induction of antibody synthesis by Th1 and Th2 types of helper T cells is discussed.
|Number of pages||8|
|State||Published - Aug 1993|
Bibliographical noteFunding Information:
This work was supported by grants AI21490, AG-05731, and a Research Career development Award to B.S. from the National Institute of Aging. Our thanks are due to Dr Alan M. Kaplan for a critical review of the manuscript.
- B cell activation
- T dependent immune response
ASJC Scopus subject areas
- Immunology and Allergy