INVESTIGADORES
RABINOVICH Gabriel Adrian
artículos
Título:
GALECTIN-3 MEDIATES INTERLEUKIN-4-INDUCED SURVIVAL AND DIFFERENTIATION OF B CELLS: FUNCTIONAL CROSS-TALK AND IMPLICATIONS DURING TRYPANOSOMA CRUZI INFECTION
Autor/es:
EVA V ACOSTA-RODRÍGUEZ;; CAROLINA L MONTES;; CLAUDIA C MOTRÁN;; ELINA I ZUNIGA;; FU-TONG LIU,; GABRIEL A. RABINOVICH,; ADRIANA GRUPPI
Revista:
JOURNAL OF IMMUNOLOGY
Editorial:
American Association of Immunologists
Referencias:
Lugar: Baltimore, MD, USA; Año: 2004 vol. 172 p. 493 - 502
ISSN:
0022-1767
Resumen:
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. Here, we provide evidence both in vitro and in vivo, showing that galectin-3 (Gal-3), a b-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 crosslinking. 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 T 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 towards a plasma cell pathway.  Moreover, B cells with restrained endogenous Gal-3 expression failed to downregulate the Blimp-1 transcription factor after IL-4 stimulation.  Finally, inhibition of Gal-3 in vivo skewed the balance towards plasma cell differentiation, which resulted in increased immunoglobulin 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.