CD40 ligand and appropriate cytokines induce switching to IgG, IgA, and IgE and coordinated germinal center and plasmacytoid phenotypic differentiation in a human monoclonal IgM+ IgD+ B cell line

Andrea Cerutti, Hong Zan, Andras Schaffer, Peter Leif Bergsagel, Nagaradona Harindranath, Edward E. Max, Paolo Casali

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

B lymphocytes are induced to undergo Ig class switching and a complex phenotypic differentiation by the milieu of the germinal center. Partly as a result of the lack of a suitable in vitro B cell model, the relationship between these processes in the humans has never been formally established in vitro. We have identified a human monoclonal B cell line, CL-01, that expresses surface IgM and IgD and, upon induction with CD40 ligand, IL-4, and IL-10, switches to all seven downstream isotypes, showing typical DNA switch recombination preceded by germline transcription of targeted C(H) regions. In CL-01 cells, switch-inducing stimuli trigger concomitant changes in expression of surface IgD, CD23, CD38, and CD77 that parallel those reported in ex vivo isolated tonsillar centroblasts, centrocytes, and memory B cells. Eventually, in the presence of IL-6, CL-01 cells express CD56 and accumulate cytoplasmic IgG and IgA, both traits of plasmacytoid differentiation. Analysis of transcription and recombination of the Ig H locus in sorted CL- 01 cells suggest that Ig class switching begins in centroblasts, it extends to all isotypes in centrocytes, and it is extinct in memory B cells. Thus, we have induced coordinated Ig class switching, progression through germinal center phenotypic stages, and differentiation to memory B cells and plasma cells at the level of a single B clonotype. Our data suggest that these processes are likely regulated by a common maturation program, the activation of which may require CD40 ligand, IL-4, IL-10, and IL-6 only.

Original languageEnglish (US)
Pages (from-to)2145-2157
Number of pages13
JournalJournal of Immunology
Volume160
Issue number5
StatePublished - Mar 1 1998
Externally publishedYes

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Immunoglobulin D
CD40 Ligand
Germinal Center
Immunoglobulin A
Immunoglobulin E
Immunoglobulin M
B-Lymphocytes
Immunoglobulin G
Immunoglobulin Class Switching
Cytokines
Cell Line
Interleukin-4
Interleukin-10
Genetic Recombination
Interleukin-6
Switch Genes
Plasma Cells
DNA

ASJC Scopus subject areas

  • Immunology

Cite this

CD40 ligand and appropriate cytokines induce switching to IgG, IgA, and IgE and coordinated germinal center and plasmacytoid phenotypic differentiation in a human monoclonal IgM+ IgD+ B cell line. / Cerutti, Andrea; Zan, Hong; Schaffer, Andras; Bergsagel, Peter Leif; Harindranath, Nagaradona; Max, Edward E.; Casali, Paolo.

In: Journal of Immunology, Vol. 160, No. 5, 01.03.1998, p. 2145-2157.

Research output: Contribution to journalArticle

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abstract = "B lymphocytes are induced to undergo Ig class switching and a complex phenotypic differentiation by the milieu of the germinal center. Partly as a result of the lack of a suitable in vitro B cell model, the relationship between these processes in the humans has never been formally established in vitro. We have identified a human monoclonal B cell line, CL-01, that expresses surface IgM and IgD and, upon induction with CD40 ligand, IL-4, and IL-10, switches to all seven downstream isotypes, showing typical DNA switch recombination preceded by germline transcription of targeted C(H) regions. In CL-01 cells, switch-inducing stimuli trigger concomitant changes in expression of surface IgD, CD23, CD38, and CD77 that parallel those reported in ex vivo isolated tonsillar centroblasts, centrocytes, and memory B cells. Eventually, in the presence of IL-6, CL-01 cells express CD56 and accumulate cytoplasmic IgG and IgA, both traits of plasmacytoid differentiation. Analysis of transcription and recombination of the Ig H locus in sorted CL- 01 cells suggest that Ig class switching begins in centroblasts, it extends to all isotypes in centrocytes, and it is extinct in memory B cells. Thus, we have induced coordinated Ig class switching, progression through germinal center phenotypic stages, and differentiation to memory B cells and plasma cells at the level of a single B clonotype. Our data suggest that these processes are likely regulated by a common maturation program, the activation of which may require CD40 ligand, IL-4, IL-10, and IL-6 only.",
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AU - Casali, Paolo

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