Galectin-3 Mediates IL-4-Induced Survival and Differentiation of B Cells

Functional Cross-Talk and Implications during Trypanosoma cruzi Infection

Eva V. Acosta-Rodríguez, Carolina L. Montes, Claudia C. Motrán, Elina I. Zuniga, Fu-Tong Liu, Gabriel A. Rabinovich, Adriana Gruppi

Research output: Contribution to journalArticle

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Abstract

The role of transcription factors in B cell survival and differentiation has been delineated during the last years. However, little is known about the intermediate signals and the intracellular pathways that control these events. In this study, we provide evidence both in vitro and in vivo, showing that galectin-3 (Gal-3), a β-galactoside-binding protein, is a critical mediator of B cell differentiation and survival. Although Gal-3 is not expressed in resting B cells from normal mice, its expression is markedly induced after activation with stimuli such as IL-4 and CD40 cross-linking. These signals promote survival and block the final differentiation of these cells, thus allowing the rising of a memory B cell phenotype. In addition, Gal-3 is expressed in B cells from Trypanosoma cruzi-infected mice, which received signals for activation and differentiation in vivo. By using an antisense strategy, we determined that Gal-3 is a critical signal mediating the effects of IL-4 on B cell fate. Blockade of intracellular Gal-3 in vitro abrogated IL-4-induced survival of activated B cells, favoring the differentiation toward a plasma cell pathway. Moreover, B cells with restrained endogenous Gal-3 expression failed to down-regulate the Blimp-1 transcription factor after IL-4 stimulation. Finally, inhibition of Gal-3 in vivo skewed the balance toward plasma cell differentiation, which resulted in increased Ig production and parasite clearance during T. cruzi infection. Thus, the present study provides evidence of a novel role for Gal-3 as an intracellular mediator of B cell survival and a checkpoint in IL-4-induced B cell commitment toward a memory phenotype.

Original languageEnglish (US)
Pages (from-to)493-502
Number of pages10
JournalJournal of Immunology
Volume172
Issue number1
StatePublished - Jan 1 2004

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Galectin 3
Trypanosoma cruzi
Interleukin-4
B-Lymphocytes
Infection
Cell Differentiation
Cell Survival
Plasma Cells
Transcription Factors
Phenotype
Galactosides
Signal Transduction
Carrier Proteins
Parasites
Down-Regulation

ASJC Scopus subject areas

  • Immunology

Cite this

Acosta-Rodríguez, E. V., Montes, C. L., Motrán, C. C., Zuniga, E. I., Liu, F-T., Rabinovich, G. A., & Gruppi, A. (2004). Galectin-3 Mediates IL-4-Induced Survival and Differentiation of B Cells: Functional Cross-Talk and Implications during Trypanosoma cruzi Infection. Journal of Immunology, 172(1), 493-502.

Galectin-3 Mediates IL-4-Induced Survival and Differentiation of B Cells : Functional Cross-Talk and Implications during Trypanosoma cruzi Infection. / Acosta-Rodríguez, Eva V.; Montes, Carolina L.; Motrán, Claudia C.; Zuniga, Elina I.; Liu, Fu-Tong; Rabinovich, Gabriel A.; Gruppi, Adriana.

In: Journal of Immunology, Vol. 172, No. 1, 01.01.2004, p. 493-502.

Research output: Contribution to journalArticle

Acosta-Rodríguez, EV, Montes, CL, Motrán, CC, Zuniga, EI, Liu, F-T, Rabinovich, GA & Gruppi, A 2004, 'Galectin-3 Mediates IL-4-Induced Survival and Differentiation of B Cells: Functional Cross-Talk and Implications during Trypanosoma cruzi Infection', Journal of Immunology, vol. 172, no. 1, pp. 493-502.
Acosta-Rodríguez EV, Montes CL, Motrán CC, Zuniga EI, Liu F-T, Rabinovich GA et al. Galectin-3 Mediates IL-4-Induced Survival and Differentiation of B Cells: Functional Cross-Talk and Implications during Trypanosoma cruzi Infection. Journal of Immunology. 2004 Jan 1;172(1):493-502.
Acosta-Rodríguez, Eva V. ; Montes, Carolina L. ; Motrán, Claudia C. ; Zuniga, Elina I. ; Liu, Fu-Tong ; Rabinovich, Gabriel A. ; Gruppi, Adriana. / Galectin-3 Mediates IL-4-Induced Survival and Differentiation of B Cells : Functional Cross-Talk and Implications during Trypanosoma cruzi Infection. In: Journal of Immunology. 2004 ; Vol. 172, No. 1. pp. 493-502.
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