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J Exp Med. 1996 July 1; 184(1): 277–281.
PMCID: PMC2192686

B cell differentiation and isotype switching is related to division cycle number


The mature, resting immunoglobulin (Ig) M, IgD+ B lymphocyte can be induced by T cells to proliferate, switch isotype, and differentiate into Ig-secreting or memory cells. Furthermore, B cell activation results in the de novo expression or loss of a number of cell surface molecules that function in cell recirculation or further interaction with T cells. Here, a novel fluorescent technique reveals that T- dependent B cell activation induces cell surface changes that correlate with division cycle number. Furthermore, striking stepwise changes are often centered on a single round of cell division. Particularly marked was the consistent increase in IgG1+ B cells after the second division cycle, from an initial level of < 3% IgG1+ to a plateau of approximately 40% after six cell divisions. The relationship between the percentage of IgG1+ B cells and division number was independent of time after stimulation, indicating a requirement for cell division in isotype switching. IgD expression became negative after four divisions, and a number of changes centered on the sixth division, including the loss of IgM, CD23, and B220. The techniques used here should prove useful for tracking other differentiation pathways and for future analysis of the molecular events associated with stepwise differentiation at the single cell level.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Parker DC. T cell-dependent B cell activation. Annu Rev Immunol. 1993;11:331–360. [PubMed]
  • Snapper CM, Paul WE. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. [PubMed]
  • Coffman RL, Lebman DA, Rothman P. Mechanism and regulation of immunoglobulin isotype switching. Adv Immunol. 1993;54:229–270. [PubMed]
  • Dunnick W, Wilson M, Stavnezer J. Mutations, duplication, and deletion of recombined switch regions suggest a role for DNA replication in the immunoglobulin heavy-chain switch. Mol Cell Biol. 1989 May;9(5):1850–1856. [PMC free article] [PubMed]
  • Dunnick W, Stavnezer J. Copy choice mechanism of immunoglobulin heavy-chain switch recombination. Mol Cell Biol. 1990 Jan;10(1):397–400. [PMC free article] [PubMed]
  • Lundgren M, Ström L, Bergquist LO, Skog S, Heiden T, Stavnezer J, Severinson E. Cell cycle regulation of immunoglobulin class switch recombination and germ-line transcription: potential role of Ets family members. Eur J Immunol. 1995 Jul;25(7):2042–2051. [PubMed]
  • van der Loo W, Gronowicz ES, Strober S, Herzenberg LA. Cell differentiation in the presence of cytochalasin B: studies on the "switch" to IgG secretion after polyclonal B cell activation. J Immunol. 1979 Apr;122(4):1203–1208. [PubMed]
  • Kenter AL, Watson JV. Cell cycle kinetics model of LPS-stimulated spleen cells correlates switch region rearrangements with S phase. J Immunol Methods. 1987 Feb 26;97(1):111–117. [PubMed]
  • Lyons AB, Parish CR. Determination of lymphocyte division by flow cytometry. J Immunol Methods. 1994 May 2;171(1):131–137. [PubMed]
  • Hodgkin PD, Yamashita LC, Coffman RL, Kehry MR. Separation of events mediating B cell proliferation and Ig production by using T cell membranes and lymphokines. J Immunol. 1990 Oct 1;145(7):2025–2034. [PubMed]
  • Hodgkin PD, Yamashita LC, Seymour B, Coffman RL, Kehry MR. Membranes from both Th1 and Th2 T cell clones stimulate B cell proliferation and prepare B cells for lymphokine-induced differentiation to secrete Ig. J Immunol. 1991 Dec 1;147(11):3696–3702. [PubMed]
  • Hodgkin PD, Castle BE, Kehry MR. B cell differentiation induced by helper T cell membranes: evidence for sequential isotype switching and a requirement for lymphokines during proliferation. Eur J Immunol. 1994 Jan;24(1):239–246. [PubMed]
  • Camp RL, Kraus TA, Birkeland ML, Puré E. High levels of CD44 expression distinguish virgin from antigen-primed B cells. J Exp Med. 1991 Mar 1;173(3):763–766. [PMC free article] [PubMed]
  • Lesley J, Hyman R, Kincade PW. CD44 and its interaction with extracellular matrix. Adv Immunol. 1993;54:271–335. [PubMed]
  • Lalor PA, Nossal GJ, Sanderson RD, McHeyzer-Williams MG. Functional and molecular characterization of single, (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific, IgG1+ B cells from antibody-secreting and memory B cell pathways in the C57BL/6 immune response to NP. Eur J Immunol. 1992 Nov;22(11):3001–3011. [PubMed]

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