Regulation of antibody response in vitro. X. Biphasic effect of cyclic AMP on the secondary anti hapten antibody response to anti immunoglobulin and enhancing soluble factor

T. Kishimoto, K. Ishizaka

Research output: Contribution to journalArticle

Abstract

The effect of elevation of an intracellular cyclic AMP level on in vitro anti hapten antibody response was studied, by using mesenteric lymph node cells of rabbits which were primed with dinitrophenylated Ascaris antigen (DNP Asc) or DNP ragweed antigen (DNP Rag). The anti hapten antibody response was induced by stimulation of the primed B cells by either DNP heterologous carrier conjugate or anti immunoglobulin (anti Ig) for 24 hr (first stage), followed by 6 day culture of the activated cells in the presence of nonspecific enhancing factor (second stage). The stimulation with anti Ig induced IgG anti hapten antibody response and enhanced the formation of total IgG. Addition of dibutyryl cyclic AMP or aminophylline with anti Ig or DNP heterologous carrier during the first stage enhanced IgG anti hapten antibody response. The optimal concentration of these reagents for the enhancement was 5x10-4M to 10-3M. The presence of 5x10-6 M prostaglandin E1 during the first stage also enhanced the antibody response. Similarly, the presence of dibutyryl cyclic AMP or aminophylline during the stimulation of DNP Rag primed cells with homologous antigen (first stage) enhanced the antibody response. If the same concentration of dibutyryl cyclic AMP or aminophylline was added together with enhancing soluble factor during the second stage after the stimulation of the primed cells with anti Ig, both the antibody response and the formation of IgG were suppressed. The antibody response of DNP Rag primed cells stimulated with homologous antigen was also suppressed if dibutyryl cyclic AMP or aminophylline was added during the subsequent culture (second stage). Evidence was obtained that suppression of antibody response by cyclic AMP during the second stage is probably due to inhibition of the proliferation of B cells. Neither of these drugs suppressed the formation of enhancing soluble factor from the carrier specific cells stimulated with the homologous carrier. The results obtained in the present experiments suggested that stimulation of hapten primed B cells with anti γ chain in the presence of an optimal concentration of dibutyryl cyclic AMP resulted in the formation of a significant amount of IgG anti DNP antibody without participation of T cells.

Original languageEnglish (US)
Pages (from-to)534-541
Number of pages8
JournalJournal of Immunology
Volume116
Issue number2
StatePublished - Dec 1 1976

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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