Blimp-1 over-expression abrogates IL-4- and CD40-mediated suppression of terminal B cell differentiation but arrests isotype switching

Eur J Immunol. 2001 Jul;31(7):1972-80. doi: 10.1002/1521-4141(200107)31:7<1972::aid-immu1972>;2-t.


Following stimulation, primary B cells either directly undergo terminal differentiation to IgM-secreting plasma cells or enter the memory pathway characterized by affinity maturation and isotype switching. Which of the various fates is adopted by B cells is determined by the strength and duration of the antigenic signal, the availability and quality of T cell help and additional signals derived from the germinal center milieu. High rate secretion is correlated with endogenous Blimp-1 levels and can be caused by ectopic expression of Blimp-1. Using cultures of resting primary mouse B cells stimulated in vitro in various combinations with IL-4, anti-mu F(ab')2 or anti-CD40 in the absence or presence of lipopolysaccharide, we show that IgM secretion and the expression of Blimp-1 is either not induced or even suppressed by B cell receptors (BCR) or CD40 ligation and by IL-4. Additional treatment with IL-2 and IL-5 induces Blimp-1 expression and facilitates IgM and IgG1 secretion, which can also be achieved by retroviral transduction of Blimp-1. On the other hand, the drastic increase in membrane IgG1(+) cells with time in cultures treated with IL-4 is greatly diminished in cells forced to express Blimp-1. We conclude that suppression of Blimp-1 by antigen-BCR interaction and T helper cell-dependent CD40 and IL-4 signaling are necessary to facilitate entrance into the memory pathway and to prevent terminal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • CD40 Antigens / immunology
  • CD40 Antigens / physiology*
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Immunoglobulin Class Switching*
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin M / biosynthesis
  • Interleukin-2 / pharmacology
  • Interleukin-4 / pharmacology*
  • Interleukin-5 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Positive Regulatory Domain I-Binding Factor 1
  • RNA, Messenger / biosynthesis
  • Repressor Proteins*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Up-Regulation


  • CD40 Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-2
  • Interleukin-5
  • Lipopolysaccharides
  • Prdm1 protein, mouse
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • Interleukin-4
  • Positive Regulatory Domain I-Binding Factor 1