B Cell Differentiation Factor-Induced B Cell Maturation: Regulation via Reduction in cAMP

Ruoqing Huang, Jillian Cioffi, Kelly A Berg, Roger London, Michal Cidon, Saul Maayani, Lloyd Mayer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We have previously described a novel human B cell differentiation factor (BCDF), 446-BCDF, that is distinct biochemically and functionally from other cytokines. Since signal transduction pathways involved in human B cell differentiation have been incompletely studied and are poorly understood, we assessed the effects of 446-BCDF on various intracellular second messenger systems. After exposure of B cells to 446-BCDF, intracellular cAMP concentration started to decrease at 5 min and was significantly lower at 30 min and reached the lowest level at 4 hr. In most cases, cAMP concentrations returned toward baseline by 24 hr. A cAMP analog (dibutyryl cAMP), a stimulator of adenyl cyclase (forskolin), and phosphodiesterase inhibitors (aminophylline and IBMX) which inhibited the 446-BCDF-induced decrease in intracellular cAMP, inhibited 446-BCDF-induced B cell differentiation, suggesting that the fall in intracellular cAMP was a critical event in this process. To understand the mechanism involved in the reduction of cAMP, B cells were treated with pertussis toxin (PTX), a Gi protein inhibitor. Pertussis toxin blocked 446-BCDF-induced B cell differentiation as well, suggesting that 446-BCDF may function by stimulation of a Gi-linked receptor resulting in the inhibition of adenylate cyclase with a consequent reduction in cAMP. Other cytokines known to promote Ig secretion (IL2 and IL6) also caused a reduction in cAMP, suggesting that this pathway may be generally important in B cell differentiation. Taken together, these data suggest that at least one pathway of terminal maturation in B cells may involve the reduction of intracellular cAMP.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalCellular Immunology
Volume162
Issue number1
DOIs
StatePublished - Apr 15 1995
Externally publishedYes

Fingerprint

Interleukin-6
B-Lymphocytes
Cell Differentiation
Pertussis Toxin
Second Messenger Systems
Adenylyl Cyclases
Cytokines
1-Methyl-3-isobutylxanthine
Aminophylline
Phosphodiesterase Inhibitors
Colforsin
Interleukin-2
Signal Transduction
Proteins

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Huang, R., Cioffi, J., Berg, K. A., London, R., Cidon, M., Maayani, S., & Mayer, L. (1995). B Cell Differentiation Factor-Induced B Cell Maturation: Regulation via Reduction in cAMP. Cellular Immunology, 162(1), 49-55. https://doi.org/10.1006/cimm.1995.1050

B Cell Differentiation Factor-Induced B Cell Maturation : Regulation via Reduction in cAMP. / Huang, Ruoqing; Cioffi, Jillian; Berg, Kelly A; London, Roger; Cidon, Michal; Maayani, Saul; Mayer, Lloyd.

In: Cellular Immunology, Vol. 162, No. 1, 15.04.1995, p. 49-55.

Research output: Contribution to journalArticle

Huang, R, Cioffi, J, Berg, KA, London, R, Cidon, M, Maayani, S & Mayer, L 1995, 'B Cell Differentiation Factor-Induced B Cell Maturation: Regulation via Reduction in cAMP', Cellular Immunology, vol. 162, no. 1, pp. 49-55. https://doi.org/10.1006/cimm.1995.1050
Huang, Ruoqing ; Cioffi, Jillian ; Berg, Kelly A ; London, Roger ; Cidon, Michal ; Maayani, Saul ; Mayer, Lloyd. / B Cell Differentiation Factor-Induced B Cell Maturation : Regulation via Reduction in cAMP. In: Cellular Immunology. 1995 ; Vol. 162, No. 1. pp. 49-55.
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