Elevated levels of intracellular cAMP sensitize resting B lymphocytes to immune complex‐induced unresponsiveness

Sidney Stein, Richard P. Phipps

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The ability of immune complexes (IC) to regulate B lymphocyte differentiation was investigated. Using an in vitro model, we previously demonstrated that macrophages (MΦ) or lymphoid dendritic cells pulsed with IC differentially regulated B cell function, inducing unresponsiveness or stimulation, respectively. The capacity of MΦ to induce unresponsiveness was dependent upon two signals, an antigen‐specific one supplied by the IC and MΦ‐secreted prostaglandin (PG)E2. Total inhibition of antibody production was never achieved as a small percentage of B lymphocytes were resistant to IC‐induced unresponsiveness. In this study, utilizing an accessory cell‐free system, we demonstrate that splenic B cell fractions separated on Percoll density gradients are heterogeneous in their sensitivity to IC‐mediated unresponsiveness. Small resting B lymphocytes are exquisitely sensitive to IC‐mediated negative signaling and exhibit virtual total ablation of antibody responses. Conversely, large activated B cells are more refractory to this inhibitory pathway. PGE2 and other agents which elevate cAMP potentiate IC‐induced unresponsiveness in resting, but not activated B lymphocytes. In addition treatment of resting B cells with PGF, which did not elevate cAMP, failed to sensitize these cells to IC‐mediated negative signaling. Unresponsiveness induced by IC is selective for specific aspects of B lymphocyte activation, since B cell differentiation but not proliferation is affected. Furthermore, pre‐treatment of resting B lymphocytes with interleukin 4 prevents the IC‐induced ablation of IgM antibody responses. Overall, our results indicate that the binding of IC by resting B lymphocytes provides a potent mechanism for inhibiting differentiation without affecting proliferation. These observations suggest that in vivo, IC play an important role in regulating the memory B lymphocyte pathway.

Original languageEnglish (US)
Pages (from-to)313-318
Number of pages6
JournalEuropean Journal of Immunology
Volume21
Issue number2
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

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B-Lymphocytes
Antigen-Antibody Complex
Antibody Formation
Dinoprostone
Dinoprost
Cell-Free System
Lymphocyte Activation
Interleukin-4
Dendritic Cells
Immunoglobulin M
Cell Differentiation
Macrophages
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Elevated levels of intracellular cAMP sensitize resting B lymphocytes to immune complex‐induced unresponsiveness. / Stein, Sidney; Phipps, Richard P.

In: European Journal of Immunology, Vol. 21, No. 2, 01.01.1991, p. 313-318.

Research output: Contribution to journalArticle

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